TWI736578B - 6-5元稠合唑環衍生物及其藥物組合物，以及作為藥物的應用 - Google Patents

6-5元稠合唑環衍生物及其藥物組合物，以及作為藥物的應用 Download PDF

Info

Publication number: TWI736578B
Authority: TW; Taiwan
Prior art keywords: methyl; pyridin; amine; alkyl; isopropyl
Prior art date: 2016-02-06

Application number

TW106103864A

Other languages

English (en)

Chinese (zh)

Other versions

TW201801729A (zh

Inventor

趙興東

同雙李

周祖文

王憲龍

陳嶺

容悅

劉啟洪

陳志方

張華傑

譚銳

譚浩瀚

李志福

張衛鵬

姜立花

劉研新

令狐莉

林敏�

孫婧

為波王

Original Assignee

大陸商上海複尚慧創醫藥研究有限公司

大陸商重慶複創醫藥研究有限公司

Priority date (The priority date 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 date listed.)

2016-02-06

Filing date

2017-02-06

Publication date

2021-08-21

2017-02-06 Application filed by 大陸商上海複尚慧創醫藥研究有限公司, 大陸商重慶複創醫藥研究有限公司 filed Critical 大陸商上海複尚慧創醫藥研究有限公司

2018-01-16 Publication of TW201801729A publication Critical patent/TW201801729A/zh

2021-08-21 Application granted granted Critical

2021-08-21 Publication of TWI736578B publication Critical patent/TWI736578B/zh

Links

229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title 1
239000003909 protein kinase inhibitor Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 188
150000003839 salts Chemical class 0.000 claims abstract description 86
239000003814 drug Substances 0.000 claims abstract description 42
101000715943 Caenorhabditis elegans Cyclin-dependent kinase 4 homolog Proteins 0.000 claims abstract description 24
125000000217 alkyl group Chemical group 0.000 claims description 226
LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 claims description 81
125000001072 heteroaryl group Chemical group 0.000 claims description 67
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 49
125000001424 substituent group Chemical group 0.000 claims description 40
229910052739 hydrogen Inorganic materials 0.000 claims description 33
239000001257 hydrogen Substances 0.000 claims description 33
229910052736 halogen Inorganic materials 0.000 claims description 31
150000002367 halogens Chemical class 0.000 claims description 31
238000011282 treatment Methods 0.000 claims description 25
229940079593 drug Drugs 0.000 claims description 22
239000008194 pharmaceutical composition Substances 0.000 claims description 22
239000000126 substance Substances 0.000 claims description 17
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 17
238000002360 preparation method Methods 0.000 claims description 12
229940124597 therapeutic agent Drugs 0.000 claims description 11
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 8
230000002265 prevention Effects 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
230000005764 inhibitory process Effects 0.000 claims description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
230000002159 abnormal effect Effects 0.000 claims description 4
230000004663 cell proliferation Effects 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
230000006872 improvement Effects 0.000 claims description 4
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 3
WXXDYJWVVZUDKA-UHFFFAOYSA-N N-[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]-5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound C(C)N1CCN(CC1)CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C1=CC=2C(N=C1)=NN(C=2C(C)C)C)F WXXDYJWVVZUDKA-UHFFFAOYSA-N 0.000 claims description 3
NZJMHSTXIXCELC-OAQYLSRUSA-N N-[5-[[(8aR)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]methyl]pyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1C[C@@H]2N(CC1)CCC2)C=1C=C2C(=NC=1)N=C(N2C(C)C)C NZJMHSTXIXCELC-OAQYLSRUSA-N 0.000 claims description 3
MLXKGRKGLLBNRE-FQEVSTJZSA-N 4-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)-5-fluoro-N-[5-[[(3S)-3-(methoxymethyl)-4-methylpiperazin-1-yl]methyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C(C)(C)(C)C=1N(N=C2N=CC(=CC2=1)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1C[C@H](N(CC1)C)COC)C MLXKGRKGLLBNRE-FQEVSTJZSA-N 0.000 claims description 2
RHXRAKXKHNWBSI-UHFFFAOYSA-N 4-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)-N-[5-[(3-ethyl-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl]pyridin-2-yl]-5-fluoropyrimidin-2-amine Chemical compound C(C)(C)(C)C=1N(N=C2N=CC(=CC2=1)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1C2CN(CC1CC2)CC)C RHXRAKXKHNWBSI-UHFFFAOYSA-N 0.000 claims description 2
LXWBWBJMRYBYLJ-UHFFFAOYSA-N N-[4-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)-5-fluoropyrimidin-2-yl]-6-ethyl-7,8-dihydro-5H-1,6-naphthyridin-2-amine Chemical compound C(C)(C)(C)C=1N(N=C2N=CC(=CC2=1)C1=NC(=NC=C1F)NC1=NC=2CCN(CC=2C=C1)CC)C LXWBWBJMRYBYLJ-UHFFFAOYSA-N 0.000 claims description 2
NZJMHSTXIXCELC-NRFANRHFSA-N N-[5-[[(8aS)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]methyl]pyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1C[C@H]2N(CC1)CCC2)C=1C=C2C(=NC=1)N=C(N2C(C)C)C NZJMHSTXIXCELC-NRFANRHFSA-N 0.000 claims description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
UPCPDAQDMQXBSS-UHFFFAOYSA-N 4-(1-tert-butyl-2-methylimidazo[4,5-b]pyridin-6-yl)-N-[5-[(8-ethyl-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl]pyridin-2-yl]-5-fluoropyrimidin-2-amine Chemical compound C(C)(C)(C)N1C(=NC2=NC=C(C=C21)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1CC2CCC(C1)N2CC)C UPCPDAQDMQXBSS-UHFFFAOYSA-N 0.000 claims 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 49
201000010099 disease Diseases 0.000 abstract description 41
230000000694 effects Effects 0.000 abstract description 13
230000002062 proliferating effect Effects 0.000 abstract description 12
206010028980 Neoplasm Diseases 0.000 abstract description 9
201000011510 cancer Diseases 0.000 abstract description 6
206010061218 Inflammation Diseases 0.000 abstract description 3
230000004054 inflammatory process Effects 0.000 abstract description 3
-1 2-methylbutenyl Chemical group 0.000 description 156
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
125000000623 heterocyclic group Chemical group 0.000 description 84
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 82
239000000203 mixture Substances 0.000 description 76
125000003118 aryl group Chemical group 0.000 description 71
125000000304 alkynyl group Chemical group 0.000 description 60
125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 48
239000000543 intermediate Substances 0.000 description 46
239000000243 solution Substances 0.000 description 44
238000000034 method Methods 0.000 description 43
125000000753 cycloalkyl group Chemical group 0.000 description 39
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 37
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 37
125000004432 carbon atom Chemical group C* 0.000 description 35
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 35
125000006374 C2-C10 alkenyl group Chemical group 0.000 description 32
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
125000003545 alkoxy group Chemical group 0.000 description 31
235000019439 ethyl acetate Nutrition 0.000 description 29
125000003342 alkenyl group Chemical group 0.000 description 28
125000004414 alkyl thio group Chemical group 0.000 description 28
125000000000 cycloalkoxy group Chemical group 0.000 description 28
125000005366 cycloalkylthio group Chemical group 0.000 description 28
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 27
150000002431 hydrogen Chemical class 0.000 description 27
229910052757 nitrogen Inorganic materials 0.000 description 27
125000003282 alkyl amino group Chemical group 0.000 description 26
125000006310 cycloalkyl amino group Chemical group 0.000 description 26
239000011734 sodium Substances 0.000 description 26
229910052717 sulfur Inorganic materials 0.000 description 26
238000006243 chemical reaction Methods 0.000 description 25
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 21
229910052760 oxygen Inorganic materials 0.000 description 20
238000010898 silica gel chromatography Methods 0.000 description 20
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
125000004429 atom Chemical group 0.000 description 19
125000005842 heteroatom Chemical group 0.000 description 19
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
229910052799 carbon Inorganic materials 0.000 description 18
239000003480 eluent Substances 0.000 description 17
239000002253 acid Substances 0.000 description 16
125000006239 protecting group Chemical group 0.000 description 16
238000001308 synthesis method Methods 0.000 description 16
UOIMSYSBTIGWJJ-UHFFFAOYSA-N tert-butyl 4-[(6-aminopyridin-3-yl)methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC1=CC=C(N)N=C1 UOIMSYSBTIGWJJ-UHFFFAOYSA-N 0.000 description 16
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
239000011593 sulfur Chemical group 0.000 description 15
125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
208000024891 symptom Diseases 0.000 description 14
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 13
210000004027 cell Anatomy 0.000 description 13
239000003112 inhibitor Substances 0.000 description 13
239000001301 oxygen Substances 0.000 description 13
238000003786 synthesis reaction Methods 0.000 description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
239000004480 active ingredient Substances 0.000 description 11
230000008901 benefit Effects 0.000 description 11
230000015572 biosynthetic process Effects 0.000 description 11
238000006467 substitution reaction Methods 0.000 description 11
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 10
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
239000002585 base Substances 0.000 description 10
WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
238000010189 synthetic method Methods 0.000 description 10
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
239000004615 ingredient Substances 0.000 description 9
239000007787 solid Substances 0.000 description 9
102000003903 Cyclin-dependent kinases Human genes 0.000 description 8
108090000266 Cyclin-dependent kinases Proteins 0.000 description 8
239000011203 carbon fibre reinforced carbon Substances 0.000 description 8
208000035475 disorder Diseases 0.000 description 8
230000002401 inhibitory effect Effects 0.000 description 8
239000000047 product Substances 0.000 description 8
NJSKBCIZXYIRPY-UHFFFAOYSA-N (1-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)boronic acid Chemical compound C(C)(C)C1=NN(C2=NC=C(C=C21)B(O)O)C NJSKBCIZXYIRPY-UHFFFAOYSA-N 0.000 description 7
IJQYADFIFAUUFR-UHFFFAOYSA-N 1-(5-bromo-2-chloropyridin-3-yl)-2-methylpropan-1-one Chemical compound BrC=1C=C(C(=NC=1)Cl)C(C(C)C)=O IJQYADFIFAUUFR-UHFFFAOYSA-N 0.000 description 7
YGPYNLZCNDPHTQ-UHFFFAOYSA-N 5-bromo-2-chloropyridine-3-carbaldehyde Chemical compound ClC1=NC=C(Br)C=C1C=O YGPYNLZCNDPHTQ-UHFFFAOYSA-N 0.000 description 7
125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 7
241000124008 Mammalia Species 0.000 description 7
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
239000007864 aqueous solution Substances 0.000 description 7
238000005859 coupling reaction Methods 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
239000003921 oil Substances 0.000 description 7
235000019198 oils Nutrition 0.000 description 7
239000003208 petroleum Substances 0.000 description 7
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
239000007858 starting material Substances 0.000 description 7
239000000725 suspension Substances 0.000 description 7
230000001225 therapeutic effect Effects 0.000 description 7
QLXASFJHUCKEHU-UHFFFAOYSA-N 5-bromo-3-fluoropyridin-2-amine Chemical compound NC1=NC=C(Br)C=C1F QLXASFJHUCKEHU-UHFFFAOYSA-N 0.000 description 6
XDCYRPFADMZSFI-UHFFFAOYSA-N 5-bromo-3-tert-butyl-2H-pyrazolo[3,4-b]pyridine Chemical compound BrC=1C=C2C(=NC=1)NN=C2C(C)(C)C XDCYRPFADMZSFI-UHFFFAOYSA-N 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 6
150000001335 aliphatic alkanes Chemical group 0.000 description 6
125000003277 amino group Chemical group 0.000 description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
150000001721 carbon Chemical group 0.000 description 6
239000000460 chlorine Substances 0.000 description 6
125000004122 cyclic group Chemical group 0.000 description 6
235000014113 dietary fatty acids Nutrition 0.000 description 6
239000000194 fatty acid Substances 0.000 description 6
229930195729 fatty acid Natural products 0.000 description 6
230000004048 modification Effects 0.000 description 6
238000012986 modification Methods 0.000 description 6
125000004433 nitrogen atom Chemical group N* 0.000 description 6
229920001223 polyethylene glycol Chemical class 0.000 description 6
150000003254 radicals Chemical class 0.000 description 6
239000002904 solvent Substances 0.000 description 6
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 6
QRCIVOIEHSUADI-UHFFFAOYSA-N tert-butyl 4-[(6-bromopyridin-3-yl)methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC1=CC=C(Br)N=C1 QRCIVOIEHSUADI-UHFFFAOYSA-N 0.000 description 6
OMJCJJZDACYWCU-UHFFFAOYSA-N (3-propan-2-yl-2H-pyrazolo[3,4-b]pyridin-5-yl)boronic acid Chemical compound C(C)(C)C1=NNC2=NC=C(C=C21)B(O)O OMJCJJZDACYWCU-UHFFFAOYSA-N 0.000 description 5
OWOHLURDBZHNGG-YFKPBYRVSA-N (8ar)-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione Chemical compound O=C1CNC(=O)[C@@H]2CCCN12 OWOHLURDBZHNGG-YFKPBYRVSA-N 0.000 description 5
XCYSMZLJIAGUFC-UHFFFAOYSA-N 1-(5-bromo-2-chloropyridin-3-yl)-2,2-dimethylpropan-1-one Chemical compound BrC=1C=C(C(=NC=1)Cl)C(C(C)(C)C)=O XCYSMZLJIAGUFC-UHFFFAOYSA-N 0.000 description 5
GXEGGTKFWNXZPI-UHFFFAOYSA-N 1-(5-bromo-2-chloropyridin-3-yl)-2-methylpropan-1-ol Chemical compound BrC=1C=C(C(=NC=1)Cl)C(C(C)C)O GXEGGTKFWNXZPI-UHFFFAOYSA-N 0.000 description 5
MNJBMPQTXVZMFZ-UHFFFAOYSA-N 5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-amine Chemical compound C1CN(CC)CCN1CC1=CC=C(N)N=C1 MNJBMPQTXVZMFZ-UHFFFAOYSA-N 0.000 description 5
FDTXFVXXVRRKFM-UHFFFAOYSA-N 5-bromo-N-tert-butyl-2-nitropyridin-3-amine Chemical compound BrC=1C=C(C(=NC=1)[N+](=O)[O-])NC(C)(C)C FDTXFVXXVRRKFM-UHFFFAOYSA-N 0.000 description 5
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
150000001204 N-oxides Chemical class 0.000 description 5
239000002202 Polyethylene glycol Chemical class 0.000 description 5
125000002619 bicyclic group Chemical group 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
239000012141 concentrate Substances 0.000 description 5
238000001914 filtration Methods 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
239000010410 layer Substances 0.000 description 5
239000007788 liquid Substances 0.000 description 5
125000004430 oxygen atom Chemical group O* 0.000 description 5
RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 5
PNFFICVZQREJQA-UHFFFAOYSA-N tert-butyl 4-[[6-[[5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-yl]amino]pyridin-3-yl]methyl]piperazine-1-carboxylate Chemical compound FC=1C(=NC(=NC=1)NC1=CC=C(C=N1)CN1CCN(CC1)C(=O)OC(C)(C)C)C=1C=C2C(=NC=1)N=C(N2C(C)C)C PNFFICVZQREJQA-UHFFFAOYSA-N 0.000 description 5
ZQEBQGAAWMOMAI-ZETCQYMHSA-N (2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C(O)=O ZQEBQGAAWMOMAI-ZETCQYMHSA-N 0.000 description 4
ZZGSPGXWLOYKFH-UHFFFAOYSA-N (5-bromo-2-chloropyridin-3-yl)methanol Chemical compound OCC1=CC(Br)=CN=C1Cl ZZGSPGXWLOYKFH-UHFFFAOYSA-N 0.000 description 4
FTTATHOUSOIFOQ-ZETCQYMHSA-N (8as)-1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2CCC[C@H]21 FTTATHOUSOIFOQ-ZETCQYMHSA-N 0.000 description 4
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
JVCBVWTTXCNJBJ-UHFFFAOYSA-N 1-azabicyclo[2.2.1]heptane Chemical compound C1CC2CCN1C2 JVCBVWTTXCNJBJ-UHFFFAOYSA-N 0.000 description 4
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 4
GAIXRSXIEKWQOT-UHFFFAOYSA-N 5-(2-chloro-5-fluoropyrimidin-4-yl)-1-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridine Chemical compound ClC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N(N=C2C(C)C)C)F GAIXRSXIEKWQOT-UHFFFAOYSA-N 0.000 description 4
UZEOLJJBRRWSCG-UHFFFAOYSA-N 5-(2-chloro-5-fluoropyrimidin-4-yl)-7-fluoro-1-methyl-3-propan-2-yl-3a,7a-dihydroindazole Chemical compound ClC1=NC=C(C(=N1)C1=CC2C(=NN(C2C(=C1)F)C)C(C)C)F UZEOLJJBRRWSCG-UHFFFAOYSA-N 0.000 description 4
TTZIIUFYHSVXOO-UHFFFAOYSA-N 5-bromo-1-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridine Chemical compound C1=C(Br)C=C2C(C(C)C)=NN(C)C2=N1 TTZIIUFYHSVXOO-UHFFFAOYSA-N 0.000 description 4
MRHGOTPAKCWLTL-UHFFFAOYSA-N 5-bromo-2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridine Chemical compound N1=CC(Br)=CC2=C(C(C)C)N(C)N=C21 MRHGOTPAKCWLTL-UHFFFAOYSA-N 0.000 description 4
JZTXKNVJIAEOFL-UHFFFAOYSA-N 5-bromo-3-N-tert-butylpyridine-2,3-diamine Chemical compound BrC=1C=C(C(=NC=1)N)NC(C)(C)C JZTXKNVJIAEOFL-UHFFFAOYSA-N 0.000 description 4
YMXQSNGTVXQMLC-UHFFFAOYSA-N 5-bromo-3-fluoro-2-nitropyridine Chemical compound [O-][N+](=O)C1=NC=C(Br)C=C1F YMXQSNGTVXQMLC-UHFFFAOYSA-N 0.000 description 4
XWYBLYSOXIQCEC-UHFFFAOYSA-N 5-bromo-3-tert-butyl-2-methylpyrazolo[3,4-b]pyridine Chemical compound N1=CC(Br)=CC2=C(C(C)(C)C)N(C)N=C21 XWYBLYSOXIQCEC-UHFFFAOYSA-N 0.000 description 4
GVXZNRJLWSJQMZ-UHFFFAOYSA-N BrC=1C=C2C(=NC1)NN=C2C(C)C Chemical compound BrC=1C=C2C(=NC1)NN=C2C(C)C GVXZNRJLWSJQMZ-UHFFFAOYSA-N 0.000 description 4
229940124297 CDK 4/6 inhibitor Drugs 0.000 description 4
108091007914 CDKs Proteins 0.000 description 4
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 4
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
125000003710 aryl alkyl group Chemical group 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
239000001768 carboxy methyl cellulose Substances 0.000 description 4
230000022131 cell cycle Effects 0.000 description 4
239000012458 free base Substances 0.000 description 4
125000005456 glyceride group Chemical group 0.000 description 4
150000002430 hydrocarbons Chemical group 0.000 description 4
150000007529 inorganic bases Chemical class 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
150000007522 mineralic acids Chemical class 0.000 description 4
125000002950 monocyclic group Chemical group 0.000 description 4
150000007524 organic acids Chemical class 0.000 description 4
239000000546 pharmaceutical excipient Substances 0.000 description 4
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
239000001267 polyvinylpyrrolidone Substances 0.000 description 4
229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
238000012746 preparative thin layer chromatography Methods 0.000 description 4
239000000600 sorbitol Substances 0.000 description 4
239000003381 stabilizer Substances 0.000 description 4
238000003756 stirring Methods 0.000 description 4
125000004434 sulfur atom Chemical group 0.000 description 4
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
229910052718 tin Inorganic materials 0.000 description 4
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
ZHUNQQHNUGVFKA-UWVGGRQHSA-N (1S,4S)-2-[(6-bromopyridin-3-yl)methyl]-2,5-diazabicyclo[2.2.1]heptane Chemical compound BrC1=CC=C(C=N1)CN1[C@@H]2CN[C@H](C1)C2 ZHUNQQHNUGVFKA-UWVGGRQHSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
CKULKERWFSGWHM-UHFFFAOYSA-N 1-(5-bromo-2-chloropyridin-3-yl)-2,2-dimethylpropan-1-ol Chemical compound BrC=1C=C(C(=NC=1)Cl)C(C(C)(C)C)O CKULKERWFSGWHM-UHFFFAOYSA-N 0.000 description 3
125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 description 3
ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 3
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
MMQCTXWUZNJUTF-UHFFFAOYSA-N 5-[(4-methylpiperazin-1-yl)methyl]pyridin-2-amine Chemical compound C1CN(C)CCN1CC1=CC=C(N)N=C1 MMQCTXWUZNJUTF-UHFFFAOYSA-N 0.000 description 3
LEDIWMKGVIKUJE-RYUDHWBXSA-N 5-[[(1S,4S)-5-ethyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]methyl]pyridin-2-amine Chemical compound C(C)N1[C@@H]2CN([C@H](C1)C2)CC=1C=CC(=NC=1)N LEDIWMKGVIKUJE-RYUDHWBXSA-N 0.000 description 3
IHHHPMVCOOADKN-QWRGUYRKSA-N 5-[[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]methyl]pyridin-2-amine Chemical compound CN1[C@@H]2CN([C@H](C1)C2)CC=1C=CC(=NC=1)N IHHHPMVCOOADKN-QWRGUYRKSA-N 0.000 description 3
QBNKJVGTABFRDK-GFCCVEGCSA-N 5-[[(8aR)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]methyl]pyridin-2-amine Chemical compound C1[C@@H]2N(CCN1CC=1C=CC(=NC=1)N)CCC2 QBNKJVGTABFRDK-GFCCVEGCSA-N 0.000 description 3
QBNKJVGTABFRDK-LBPRGKRZSA-N 5-[[(8aS)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]methyl]pyridin-2-amine Chemical compound C1[C@H]2N(CCN1CC=1C=CC(=NC=1)N)CCC2 QBNKJVGTABFRDK-LBPRGKRZSA-N 0.000 description 3
NVZWMJWMTWOVNJ-UHFFFAOYSA-N 6-azaspiro[3.4]octane Chemical compound C1CCC21CNCC2 NVZWMJWMTWOVNJ-UHFFFAOYSA-N 0.000 description 3
UIWVEKSONRSDAP-UHFFFAOYSA-N 6-bromo-1-tert-butyl-2-methylimidazo[4,5-b]pyridine Chemical compound BrC=1C=C2C(=NC=1)N=C(N2C(C)(C)C)C UIWVEKSONRSDAP-UHFFFAOYSA-N 0.000 description 3
GXWNSJYVSIJRLS-UHFFFAOYSA-N 6-bromo-8-methylimidazo[1,2-a]pyrazine Chemical compound CC1=NC(Br)=CN2C=CN=C12 GXWNSJYVSIJRLS-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
241000282412 Homo Species 0.000 description 3
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
VCLLGSYJTJIQGM-STQMWFEESA-N NC1=CC=C(C=N1)CN1[C@@H]2CN([C@H](C1)C2)C(=O)OC(C)(C)C Chemical compound NC1=CC=C(C=N1)CN1[C@@H]2CN([C@H](C1)C2)C(=O)OC(C)(C)C VCLLGSYJTJIQGM-STQMWFEESA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
239000002671 adjuvant Substances 0.000 description 3
239000001506 calcium phosphate Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
239000010949 copper Substances 0.000 description 3
230000008878 coupling Effects 0.000 description 3
238000010168 coupling process Methods 0.000 description 3
239000012043 crude product Substances 0.000 description 3
229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 description 3
OWOHLURDBZHNGG-UHFFFAOYSA-N cyclo-Gly-L-Pro Natural products O=C1CNC(=O)C2CCCN12 OWOHLURDBZHNGG-UHFFFAOYSA-N 0.000 description 3
229910052805 deuterium Inorganic materials 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
125000000524 functional group Chemical group 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
229940093915 gynecological organic acid Drugs 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
150000002576 ketones Chemical class 0.000 description 3
229940043355 kinase inhibitor Drugs 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
230000001404 mediated effect Effects 0.000 description 3
201000001441 melanoma Diseases 0.000 description 3
230000002503 metabolic effect Effects 0.000 description 3
125000001624 naphthyl group Chemical group 0.000 description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
235000005985 organic acids Nutrition 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
238000007911 parenteral administration Methods 0.000 description 3
230000007170 pathology Effects 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
229910052698 phosphorus Chemical group 0.000 description 3
239000011574 phosphorus Chemical group 0.000 description 3
239000003757 phosphotransferase inhibitor Substances 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
239000000376 reactant Substances 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
238000011160 research Methods 0.000 description 3
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
238000003860 storage Methods 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
235000012222 talc Nutrition 0.000 description 3
QOMIQLRRGXOCAO-STQMWFEESA-N tert-butyl (1S,4S)-5-[(6-bromopyridin-3-yl)methyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound BrC1=CC=C(C=N1)CN1[C@@H]2CN([C@H](C1)C2)C(=O)OC(C)(C)C QOMIQLRRGXOCAO-STQMWFEESA-N 0.000 description 3
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
238000002560 therapeutic procedure Methods 0.000 description 3
238000004809 thin layer chromatography Methods 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
ZREYCSQQCSFFDH-UHFFFAOYSA-N tributyl-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)stannane Chemical compound C(C)(C)(C)C=1N(N=C2N=CC(=CC2=1)[Sn](CCCC)(CCCC)CCCC)C ZREYCSQQCSFFDH-UHFFFAOYSA-N 0.000 description 3
125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 3
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
APZCGKAVHWAPFS-QWRGUYRKSA-N (1S,4S)-2-[(6-bromopyridin-3-yl)methyl]-5-methyl-2,5-diazabicyclo[2.2.1]heptane Chemical compound BrC1=CC=C(C=N1)CN1[C@@H]2CN([C@H](C1)C2)C APZCGKAVHWAPFS-QWRGUYRKSA-N 0.000 description 2
CPTKWEIJBBDEJS-LBPRGKRZSA-N (8aS)-2-[(6-bromopyridin-3-yl)methyl]-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine Chemical compound BrC1=CC=C(C=N1)CN1C[C@H]2N(CC1)CCC2 CPTKWEIJBBDEJS-LBPRGKRZSA-N 0.000 description 2
GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
125000006033 1,1-dimethyl-2-propenyl group Chemical group 0.000 description 2
LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 2
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 description 2
OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 description 2
MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 2
125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
125000006032 3-methyl-3-butenyl group Chemical group 0.000 description 2
XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 2
JWWUDSUSOPKRRA-UHFFFAOYSA-N 5-bromo-3-N-propan-2-ylpyridine-2,3-diamine Chemical compound BrC=1C=C(C(=NC=1)N)NC(C)C JWWUDSUSOPKRRA-UHFFFAOYSA-N 0.000 description 2
IEGVJMQVMUGLMP-UHFFFAOYSA-N 5-fluoro-N-[5-[(4-methylpiperazin-1-yl)methyl]pyridin-2-yl]-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1CCN(CC1)C)C=1C=C2C(=NC=1)N=C(N2C(C)C)C IEGVJMQVMUGLMP-UHFFFAOYSA-N 0.000 description 2
QCVASANWTXPRKW-UHFFFAOYSA-N 5-fluoro-N-[5-[(4-methylpiperazin-1-yl)methyl]pyridin-2-yl]-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1CCN(CC1)C)C1=CC=2C(N=C1)=NN(C=2C(C)C)C QCVASANWTXPRKW-UHFFFAOYSA-N 0.000 description 2
KZSRXRACNDDUOO-UHFFFAOYSA-N 6-(2-chloro-5-fluoropyrimidin-4-yl)-2-methyl-1-propan-2-ylimidazo[4,5-b]pyridine Chemical compound ClC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C)F KZSRXRACNDDUOO-UHFFFAOYSA-N 0.000 description 2
OGNIIZLVRXUALR-UHFFFAOYSA-N 6-bromo-2-methyl-1-propan-2-ylimidazo[4,5-b]pyridine Chemical compound BrC=1C=C2C(=NC=1)N=C(N2C(C)C)C OGNIIZLVRXUALR-UHFFFAOYSA-N 0.000 description 2
125000003341 7 membered heterocyclic group Chemical group 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 2
206010067484 Adverse reaction Diseases 0.000 description 2
235000019489 Almond oil Nutrition 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
201000001320 Atherosclerosis Diseases 0.000 description 2
208000023275 Autoimmune disease Diseases 0.000 description 2
206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
208000026310 Breast neoplasm Diseases 0.000 description 2
KLFAIAHJLSEKFM-UHFFFAOYSA-N CC1=NC2=C(N1C(C)C)C=C(C=N2)C3=NC(=NC=C3F)NC4=NC=C(C=C4)CN5CC=NC=C5 Chemical compound CC1=NC2=C(N1C(C)C)C=C(C=N2)C3=NC(=NC=C3F)NC4=NC=C(C=C4)CN5CC=NC=C5 KLFAIAHJLSEKFM-UHFFFAOYSA-N 0.000 description 2
DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
241000282472 Canis lupus familiaris Species 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
206010009944 Colon cancer Diseases 0.000 description 2
208000035473 Communicable disease Diseases 0.000 description 2
108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 description 2
102100026804 Cyclin-dependent kinase 6 Human genes 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
229920002307 Dextran Polymers 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
101000582926 Dictyostelium discoideum Probable serine/threonine-protein kinase PLK Proteins 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
206010064571 Gene mutation Diseases 0.000 description 2
201000005569 Gout Diseases 0.000 description 2
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
229910004373 HOAc Inorganic materials 0.000 description 2
102000002812 Heat-Shock Proteins Human genes 0.000 description 2
108010004889 Heat-Shock Proteins Proteins 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
239000005909 Kieselgur Substances 0.000 description 2
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
229930182821 L-proline Natural products 0.000 description 2
206010058467 Lung neoplasm malignant Diseases 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
YEXAQVXBDYXGKW-UHFFFAOYSA-N N-[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound C(C)N1CCN(CC1)CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C)F YEXAQVXBDYXGKW-UHFFFAOYSA-N 0.000 description 2
KCRHHWXFYIFFII-OALUTQOASA-N N-[5-[[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]methyl]pyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound CC(C)n1c(C)nc2ncc(cc12)-c1nc(Nc2ccc(CN3C[C@@H]4C[C@H]3CN4)cn2)ncc1F KCRHHWXFYIFFII-OALUTQOASA-N 0.000 description 2
ZVQATGQZELGFKO-SFTDATJTSA-N N-[5-[[(1S,4S)-5-ethyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]methyl]pyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound C(C)N1[C@@H]2CN([C@H](C1)C2)CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C)F ZVQATGQZELGFKO-SFTDATJTSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
206010061535 Ovarian neoplasm Diseases 0.000 description 2
102000038030 PI3Ks Human genes 0.000 description 2
108091007960 PI3Ks Proteins 0.000 description 2
206010061902 Pancreatic neoplasm Diseases 0.000 description 2
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
208000004403 Prostatic Hyperplasia Diseases 0.000 description 2
201000004681 Psoriasis Diseases 0.000 description 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
241000283984 Rodentia Species 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
235000021355 Stearic acid Nutrition 0.000 description 2
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
208000024770 Thyroid neoplasm Diseases 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
230000006838 adverse reaction Effects 0.000 description 2
125000002009 alkene group Chemical group 0.000 description 2
125000002355 alkine group Chemical group 0.000 description 2
239000008168 almond oil Substances 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
230000033115 angiogenesis Effects 0.000 description 2
239000003963 antioxidant agent Substances 0.000 description 2
235000006708 antioxidants Nutrition 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
DXSUJCOMYMAJNG-AWEZNQCLSA-N benzyl (8as)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazine-2-carboxylate Chemical compound C([C@@H]1CCCN1CC1)N1C(=O)OCC1=CC=CC=C1 DXSUJCOMYMAJNG-AWEZNQCLSA-N 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
230000037396 body weight Effects 0.000 description 2
210000000481 breast Anatomy 0.000 description 2
RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
239000002775 capsule Substances 0.000 description 2
150000007942 carboxylates Chemical class 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
208000029742 colonic neoplasm Diseases 0.000 description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
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 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
238000001514 detection method Methods 0.000 description 2
238000011161 development Methods 0.000 description 2
230000018109 developmental process Effects 0.000 description 2
206010012601 diabetes mellitus Diseases 0.000 description 2
238000010586 diagram Methods 0.000 description 2
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 2
POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
ZQPPMHVWECSIRJ-MDZDMXLPSA-N elaidic acid Chemical compound CCCCCCCC\C=C\CCCCCCCC(O)=O ZQPPMHVWECSIRJ-MDZDMXLPSA-N 0.000 description 2
238000009505 enteric coating Methods 0.000 description 2
239000002702 enteric coating Substances 0.000 description 2
238000000105 evaporative light scattering detection Methods 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000000945 filler Substances 0.000 description 2
239000012065 filter cake Substances 0.000 description 2
238000009472 formulation Methods 0.000 description 2
239000001530 fumaric acid Substances 0.000 description 2
229960002442 glucosamine Drugs 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
239000008187 granular material Substances 0.000 description 2
239000003102 growth factor Substances 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
239000007902 hard capsule Substances 0.000 description 2
KEMQGTRYUADPNZ-UHFFFAOYSA-N heptadecanoic acid Chemical compound CCCCCCCCCCCCCCCCC(O)=O KEMQGTRYUADPNZ-UHFFFAOYSA-N 0.000 description 2
125000004415 heterocyclylalkyl group Chemical group 0.000 description 2
IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 2
PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
230000003993 interaction Effects 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
239000011630 iodine Substances 0.000 description 2
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 2
210000003734 kidney Anatomy 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000003446 ligand Substances 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
201000005202 lung cancer Diseases 0.000 description 2
208000020816 lung neoplasm Diseases 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 2
WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 2
238000002156 mixing Methods 0.000 description 2
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
125000004043 oxo group Chemical group O=* 0.000 description 2
239000005022 packaging material Substances 0.000 description 2
201000002528 pancreatic cancer Diseases 0.000 description 2
239000012188 paraffin wax Substances 0.000 description 2
230000003285 pharmacodynamic effect Effects 0.000 description 2
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 2
IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 2
RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
229920000053 polysorbate 80 Polymers 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
230000003449 preventive effect Effects 0.000 description 2
230000035755 proliferation Effects 0.000 description 2
229960002429 proline Drugs 0.000 description 2
210000002307 prostate Anatomy 0.000 description 2
235000018102 proteins Nutrition 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
238000000746 purification Methods 0.000 description 2
125000004076 pyridyl group Chemical group 0.000 description 2
230000002285 radioactive effect Effects 0.000 description 2
230000004044 response Effects 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
125000006413 ring segment Chemical group 0.000 description 2
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 2
239000008107 starch Substances 0.000 description 2
239000008117 stearic acid Substances 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000002511 suppository base Substances 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 2
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
229940126585 therapeutic drug Drugs 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
231100000331 toxic Toxicity 0.000 description 2
230000002588 toxic effect Effects 0.000 description 2
GPAPAPSPVTYEKO-UHFFFAOYSA-N tributyl-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)stannane Chemical compound C(CCC)[Sn](C=1C=C2C(=NC=1)N=C(N2C(C)C)C)(CCCC)CCCC GPAPAPSPVTYEKO-UHFFFAOYSA-N 0.000 description 2
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
SZHOJFHSIKHZHA-UHFFFAOYSA-N tridecanoic acid Chemical compound CCCCCCCCCCCCC(O)=O SZHOJFHSIKHZHA-UHFFFAOYSA-N 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
235000015112 vegetable and seed oil Nutrition 0.000 description 2
239000008158 vegetable oil Substances 0.000 description 2
239000012224 working solution Substances 0.000 description 2
CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
JDKNINBDEDWGRT-RYUDHWBXSA-N (1S,4S)-2-[(6-bromopyridin-3-yl)methyl]-5-ethyl-2,5-diazabicyclo[2.2.1]heptane Chemical compound BrC1=CC=C(C=N1)CN1[C@@H]2CN([C@H](C1)C2)CC JDKNINBDEDWGRT-RYUDHWBXSA-N 0.000 description 1
TXTWXQXDMWILOF-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl)azanium;chloride Chemical compound [Cl-].CCOC(=O)C[NH3+] TXTWXQXDMWILOF-UHFFFAOYSA-N 0.000 description 1
LGFQMLCQCHXACZ-UHFFFAOYSA-N (2-ethyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)-[6-[[5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-yl]amino]pyridin-3-yl]methanone Chemical compound C(C)N1CC2C(C1)CN(C2)C(=O)C=1C=NC(=CC=1)NC1=NC=C(C(=N1)C1=CC=2C(N=C1)=NN(C=2C(C)C)C)F LGFQMLCQCHXACZ-UHFFFAOYSA-N 0.000 description 1
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
VHYHRNYPVNFGNR-UHFFFAOYSA-N (3,5-ditert-butylphenyl)methanol Chemical compound CC(C)(C)C1=CC(CO)=CC(C(C)(C)C)=C1 VHYHRNYPVNFGNR-UHFFFAOYSA-N 0.000 description 1
FEOHYDSNGHIXOM-WLDMJGECSA-N (3R,4R,5S,6R)-3-amino-6-(hydroxymethyl)-2-methyloxane-2,4,5-triol Chemical compound CC1(O)[C@H](N)[C@@H](O)[C@H](O)[C@H](O1)CO FEOHYDSNGHIXOM-WLDMJGECSA-N 0.000 description 1
VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 1
DOUFFRZIRGUHTC-UHFFFAOYSA-N (4-ethylpiperazin-1-yl)-[6-[[5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-yl]amino]pyridin-3-yl]methanone Chemical compound C(C)N1CCN(CC1)C(=O)C=1C=NC(=CC=1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C)F DOUFFRZIRGUHTC-UHFFFAOYSA-N 0.000 description 1
CMMYBYKPLXALCJ-UHFFFAOYSA-N (8-ethyl-3,8-diazabicyclo[3.2.1]octan-3-yl)-[6-[[5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-yl]amino]pyridin-3-yl]methanone Chemical compound C(C)N1C2CN(CC1CC2)C(=O)C=1C=NC(=CC=1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C)F CMMYBYKPLXALCJ-UHFFFAOYSA-N 0.000 description 1
OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
125000000027 (C1-C10) alkoxy group Chemical group 0.000 description 1
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
DZKRDHLYQRTDBU-UPHRSURJSA-N (z)-but-2-enediperoxoic acid Chemical compound OOC(=O)\C=C/C(=O)OO DZKRDHLYQRTDBU-UPHRSURJSA-N 0.000 description 1
IIGCYQPNZRSCLY-UHFFFAOYSA-N 1,1-dimethyl-3-prop-1-enylurea Chemical compound CC=CNC(=O)N(C)C IIGCYQPNZRSCLY-UHFFFAOYSA-N 0.000 description 1
YHIIJNLSGULWAA-UHFFFAOYSA-N 1,4-thiazinane 1-oxide Chemical compound O=S1CCNCC1 YHIIJNLSGULWAA-UHFFFAOYSA-N 0.000 description 1
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 description 1
XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 description 1
FIBQTVPCVMDBRJ-UHFFFAOYSA-N 2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrol-5-yl-[6-[[5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-yl]amino]pyridin-3-yl]methanone Chemical compound FC=1C(=NC(=NC=1)NC1=CC=C(C=N1)C(=O)N1CC2CNCC2C1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C FIBQTVPCVMDBRJ-UHFFFAOYSA-N 0.000 description 1
SVNBUGZPKYWXJJ-UHFFFAOYSA-N 2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrol-5-yl-[6-[[5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-yl]amino]pyridin-3-yl]methanone Chemical compound FC=1C(=NC(=NC=1)NC1=CC=C(C=N1)C(=O)N1CC2CNCC2C1)C1=CC=2C(N=C1)=NN(C=2C(C)C)C SVNBUGZPKYWXJJ-UHFFFAOYSA-N 0.000 description 1
LWTIGYSPAXKMDG-UHFFFAOYSA-N 2,3-dihydro-1h-imidazole Chemical compound C1NC=CN1 LWTIGYSPAXKMDG-UHFFFAOYSA-N 0.000 description 1
WHPFEQUEHBULBW-UHFFFAOYSA-N 2,4-dichloro-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1Cl WHPFEQUEHBULBW-UHFFFAOYSA-N 0.000 description 1
BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
229940013085 2-diethylaminoethanol Drugs 0.000 description 1
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
JKIFPWHZEZQCQA-UHFFFAOYSA-N 2-nitrobenzenethiol Chemical compound [O-][N+](=O)C1=CC=CC=C1S JKIFPWHZEZQCQA-UHFFFAOYSA-N 0.000 description 1
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
ZVMLJQKAIDIPRT-UHFFFAOYSA-N 3,8-diazabicyclo[3.2.1]octan-3-yl-[6-[[5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-yl]amino]pyridin-3-yl]methanone Chemical compound C12CN(CC(CC1)N2)C(=O)C=1C=NC(=CC=1)NC1=NC=C(C(=N1)C1=CC=2C(N=C1)=NN(C=2C(C)C)C)F ZVMLJQKAIDIPRT-UHFFFAOYSA-N 0.000 description 1
FVOSRKUKMOVUEY-UHFFFAOYSA-N 3,8-diazabicyclo[3.2.1]octan-8-yl-[6-[[5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-yl]amino]pyridin-3-yl]methanone Chemical compound C12CNCC(CC1)N2C(=O)C=1C=NC(=CC=1)NC1=NC=C(C(=N1)C1=CC=2C(N=C1)=NN(C=2C(C)C)C)F FVOSRKUKMOVUEY-UHFFFAOYSA-N 0.000 description 1
LDZJKURBUHBPFD-UHFFFAOYSA-N 3-[4-[[6-[[4-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)-5-fluoropyrimidin-2-yl]amino]pyridin-3-yl]methyl]piperazin-1-yl]propanenitrile Chemical compound C(C)(C)(C)C=1N(N=C2N=CC(=CC2=1)C1=NC(=NC=C1F)NC1=CC=C(C=N1)CN1CCN(CC1)CCC#N)C LDZJKURBUHBPFD-UHFFFAOYSA-N 0.000 description 1
WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 1
WWEINXQNCAWBPD-UHFFFAOYSA-N 3-fluoropyridin-2-amine Chemical compound NC1=NC=CC=C1F WWEINXQNCAWBPD-UHFFFAOYSA-N 0.000 description 1
LZRVQPGTFYGJTK-UHFFFAOYSA-N 4-(1-tert-butyl-2-methylimidazo[4,5-b]pyridin-6-yl)-5-chloro-N-[5-[(4-methylpiperazin-1-yl)methyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C(C)(C)(C)N1C(=NC2=NC=C(C=C21)C1=NC(=NC=C1Cl)NC1=NC=C(C=C1)CN1CCN(CC1)C)C LZRVQPGTFYGJTK-UHFFFAOYSA-N 0.000 description 1
VQNZVQWFSQQFLK-UHFFFAOYSA-N 4-(1-tert-butyl-2-methylimidazo[4,5-b]pyridin-6-yl)-5-fluoro-N-[5-[(3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C(C)(C)(C)N1C(=NC2=NC=C(C=C21)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1C2CN(CC1CC2)C)C VQNZVQWFSQQFLK-UHFFFAOYSA-N 0.000 description 1
ICMVUFVRHXEATK-UHFFFAOYSA-N 4-(1-tert-butyl-2-methylimidazo[4,5-b]pyridin-6-yl)-5-fluoro-N-[5-[(4-methylpiperazin-1-yl)methyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C(C)(C)(C)N1C(=NC2=NC=C(C=C21)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1CCN(CC1)C)C ICMVUFVRHXEATK-UHFFFAOYSA-N 0.000 description 1
PLVLTWOHVSRQFW-UHFFFAOYSA-N 4-(1-tert-butyl-2-methylimidazo[4,5-b]pyridin-6-yl)-5-fluoro-N-[5-[(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C(C)(C)(C)N1C(=NC2=NC=C(C=C21)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1CC2CCC(C1)N2C)C PLVLTWOHVSRQFW-UHFFFAOYSA-N 0.000 description 1
GUXAIKSXEWLWLW-GOSISDBHSA-N 4-(1-tert-butyl-2-methylimidazo[4,5-b]pyridin-6-yl)-5-fluoro-N-[5-[[(3R)-3-methyl-4-(oxetan-3-yl)piperazin-1-yl]methyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C(C)(C)(C)N1C(=NC2=NC=C(C=C21)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1C[C@H](N(CC1)C1COC1)C)C GUXAIKSXEWLWLW-GOSISDBHSA-N 0.000 description 1
QPXVIEKFXBBRFH-NRFANRHFSA-N 4-(1-tert-butyl-2-methylimidazo[4,5-b]pyridin-6-yl)-5-fluoro-N-[5-[[(3S)-3-(methoxymethyl)-4-methylpiperazin-1-yl]methyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C(C)(C)(C)N1C(=NC2=NC=C(C=C21)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1C[C@H](N(CC1)C)COC)C QPXVIEKFXBBRFH-NRFANRHFSA-N 0.000 description 1
GUXAIKSXEWLWLW-SFHVURJKSA-N 4-(1-tert-butyl-2-methylimidazo[4,5-b]pyridin-6-yl)-5-fluoro-N-[5-[[(3S)-3-methyl-4-(oxetan-3-yl)piperazin-1-yl]methyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C(C)(C)(C)N1C(=NC2=NC=C(C=C21)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1C[C@@H](N(CC1)C1COC1)C)C GUXAIKSXEWLWLW-SFHVURJKSA-N 0.000 description 1
LQCYWVTYFSAQBD-UHFFFAOYSA-N 4-(1-tert-butyl-2-methylimidazo[4,5-b]pyridin-6-yl)-5-fluoro-N-[5-[[4-(oxetan-3-yl)piperazin-1-yl]methyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C(C)(C)(C)N1C(=NC2=NC=C(C=C21)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1CCN(CC1)C1COC1)C LQCYWVTYFSAQBD-UHFFFAOYSA-N 0.000 description 1
YLPFCGWRMZTJTB-UHFFFAOYSA-N 4-(1-tert-butyl-2-methylimidazo[4,5-b]pyridin-6-yl)-N-[5-(3,8-diazabicyclo[3.2.1]octan-8-ylmethyl)pyridin-2-yl]-5-fluoropyrimidin-2-amine Chemical compound C12CNCC(CC1)N2CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)(C)C)C)F YLPFCGWRMZTJTB-UHFFFAOYSA-N 0.000 description 1
HNWOSAHTHYQGNJ-UHFFFAOYSA-N 4-(1-tert-butyl-2-methylimidazo[4,5-b]pyridin-6-yl)-N-[5-[(3-ethyl-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl]pyridin-2-yl]-5-fluoropyrimidin-2-amine Chemical compound C(C)(C)(C)N1C(=NC2=NC=C(C=C21)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1C2CN(CC1CC2)CC)C HNWOSAHTHYQGNJ-UHFFFAOYSA-N 0.000 description 1
JSNCGRMSIMEFBD-UHFFFAOYSA-N 4-(1-tert-butyl-2-methylimidazo[4,5-b]pyridin-6-yl)-N-[5-[1-(4-ethylpiperazin-1-yl)ethyl]pyridin-2-yl]-5-fluoropyrimidin-2-amine Chemical compound C(C)(C)(C)N1C(=NC2=NC=C(C=C21)C1=NC(=NC=C1F)NC1=NC=C(C=C1)C(C)N1CCN(CC1)CC)C JSNCGRMSIMEFBD-UHFFFAOYSA-N 0.000 description 1
SWRVWNJARPMWAG-QFIPXVFZSA-N 4-(1-tert-butyl-2-methylimidazo[4,5-b]pyridin-6-yl)-N-[5-[[(3S)-4-ethyl-3-(methoxymethyl)piperazin-1-yl]methyl]pyridin-2-yl]-5-fluoropyrimidin-2-amine Chemical compound C(C)(C)(C)N1C(=NC2=NC=C(C=C21)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1C[C@H](N(CC1)CC)COC)C SWRVWNJARPMWAG-QFIPXVFZSA-N 0.000 description 1
QMHXVMTZJOCDCD-UHFFFAOYSA-N 4-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)-5-fluoro-N-[5-(morpholin-4-ylmethyl)pyridin-2-yl]pyrimidin-2-amine Chemical compound C(C)(C)(C)C=1N(N=C2N=CC(=CC2=1)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1CCOCC1)C QMHXVMTZJOCDCD-UHFFFAOYSA-N 0.000 description 1
LKMPYLLZFKBUOG-UHFFFAOYSA-N 4-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)-5-fluoro-N-[5-[(3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C(C)(C)(C)C=1N(N=C2N=CC(=CC2=1)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1C2CN(CC1CC2)C)C LKMPYLLZFKBUOG-UHFFFAOYSA-N 0.000 description 1
LYYXBYJBHRDCMU-UHFFFAOYSA-N 4-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)-5-fluoro-N-[5-[1-(4-methylpiperazin-1-yl)ethyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C(C)(C)(C)C=1N(N=C2N=CC(=CC2=1)C1=NC(=NC=C1F)NC1=NC=C(C=C1)C(C)N1CCN(CC1)C)C LYYXBYJBHRDCMU-UHFFFAOYSA-N 0.000 description 1
XIUPOZDEVDGCIG-BGYRXZFFSA-N 4-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)-5-fluoro-N-[5-[[(1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl]methyl]pyridin-2-yl]pyrimidin-2-amine Chemical compound C(C)(C)(C)C=1N(N=C2N=CC(=CC2=1)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1C[C@H]2CC[C@@H](C1)N2C)C XIUPOZDEVDGCIG-BGYRXZFFSA-N 0.000 description 1
GYJSPJBFUCHAPW-UHFFFAOYSA-N 4-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)-N-[5-(3,8-diazabicyclo[3.2.1]octan-8-ylmethyl)pyridin-2-yl]-5-fluoropyrimidin-2-amine Chemical compound C12CNCC(CC1)N2CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C1=CC=2C(N=C1)=NN(C=2C(C)(C)C)C)F GYJSPJBFUCHAPW-UHFFFAOYSA-N 0.000 description 1
ULWUJVPFWJEXFU-UHFFFAOYSA-N 4-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)-N-[5-[1-(4-ethylpiperazin-1-yl)ethyl]pyridin-2-yl]-5-fluoropyrimidin-2-amine Chemical compound C(C)(C)(C)C=1N(N=C2N=CC(=CC2=1)C1=NC(=NC=C1F)NC1=NC=C(C=C1)C(C)N1CCN(CC1)CC)C ULWUJVPFWJEXFU-UHFFFAOYSA-N 0.000 description 1
HFAFEBQJKWPTGR-KDURUIRLSA-N 4-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)-N-[5-[[(1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl]methyl]pyridin-2-yl]-5-fluoropyrimidin-2-amine Chemical compound [C@H]12CN(C[C@H](CC1)N2)CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C1=CC=2C(N=C1)=NN(C=2C(C)(C)C)C)F HFAFEBQJKWPTGR-KDURUIRLSA-N 0.000 description 1
AJFISQCHDCKCCG-OYRHEFFESA-N 4-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)-N-[5-[[(1R,5S)-8-ethyl-3,8-diazabicyclo[3.2.1]octan-3-yl]methyl]pyridin-2-yl]-5-fluoropyrimidin-2-amine Chemical compound C(C)(C)(C)C=1N(N=C2N=CC(=CC2=1)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1C[C@H]2CC[C@@H](C1)N2CC)C AJFISQCHDCKCCG-OYRHEFFESA-N 0.000 description 1
GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
JQTMGOLZSBTZMS-UHFFFAOYSA-N 4-methylpiperazine-1-carbaldehyde Chemical compound CN1CCN(C=O)CC1 JQTMGOLZSBTZMS-UHFFFAOYSA-N 0.000 description 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
125000004606 5,6,7,8-tetrahydroisoquinolinyl group Chemical group C1(=NC=CC=2CCCCC12)* 0.000 description 1
UKNYSJCAGUXDOQ-UHFFFAOYSA-N 5-bromo-2-chloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC(Br)=CN=C1Cl UKNYSJCAGUXDOQ-UHFFFAOYSA-N 0.000 description 1
ZGDXHNOMOPXROH-UHFFFAOYSA-N 5-bromo-3-tert-butyl-1-methylpyrazolo[3,4-b]pyridine Chemical compound BrC1=CN=C2N(C)N=C(C(C)(C)C)C2=C1 ZGDXHNOMOPXROH-UHFFFAOYSA-N 0.000 description 1
YRGMYJUKFJPNPD-UHFFFAOYSA-N 5-bromopyridine-2,3-diamine Chemical compound NC1=CC(Br)=CN=C1N YRGMYJUKFJPNPD-UHFFFAOYSA-N 0.000 description 1
ZQVLPMNLLKGGIU-UHFFFAOYSA-N 5-bromopyridine-2-carbaldehyde Chemical compound BrC1=CC=C(C=O)N=C1 ZQVLPMNLLKGGIU-UHFFFAOYSA-N 0.000 description 1
IUPWWIRRDLBAIX-UHFFFAOYSA-N 5-fluoro-N-[5-[(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)methyl]pyridin-2-yl]-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1CC2CN(CC2C1)C)C=1C=C2C(=NC=1)N=C(N2C(C)C)C IUPWWIRRDLBAIX-UHFFFAOYSA-N 0.000 description 1
DAGFXCKWWJZPBO-UHFFFAOYSA-N 5-fluoro-N-[5-[(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)methyl]pyridin-2-yl]-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1CC2CN(CC2C1)C)C1=CC=2C(N=C1)=NN(C=2C(C)C)C DAGFXCKWWJZPBO-UHFFFAOYSA-N 0.000 description 1
YBVKJCABYASGDY-UHFFFAOYSA-N 5-fluoro-N-[5-[(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)sulfonyl]pyridin-2-yl]-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)S(=O)(=O)N1CC2CN(CC2C1)C)C=1C=C2C(=NC=1)N=C(N2C(C)C)C YBVKJCABYASGDY-UHFFFAOYSA-N 0.000 description 1
NJTPWWGECXFCBP-UHFFFAOYSA-N 5-fluoro-N-[5-[(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)sulfonyl]pyridin-2-yl]-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)S(=O)(=O)N1CC2CN(CC2C1)C)C1=CC=2C(N=C1)=NN(C=2C(C)C)C NJTPWWGECXFCBP-UHFFFAOYSA-N 0.000 description 1
GALNGZKEUUMJNC-UHFFFAOYSA-N 5-fluoro-N-[5-[(3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl]pyridin-2-yl]-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1C2CN(CC1CC2)C)C=1C=C2C(=NC=1)N=C(N2C(C)C)C GALNGZKEUUMJNC-UHFFFAOYSA-N 0.000 description 1
MTLRQTGOJJGTHS-UHFFFAOYSA-N 5-fluoro-N-[5-[(3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl]pyridin-2-yl]-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1C2CN(CC1CC2)C)C1=CC=2C(N=C1)=NN(C=2C(C)C)C MTLRQTGOJJGTHS-UHFFFAOYSA-N 0.000 description 1
UQZNVWOFBPGCSJ-UHFFFAOYSA-N 5-fluoro-N-[5-[(4-methylpiperazin-1-yl)methyl]pyridin-2-yl]-4-(1-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1CCN(CC1)C)C=1C=C2C(=NC=1)N(N=C2C(C)C)C UQZNVWOFBPGCSJ-UHFFFAOYSA-N 0.000 description 1
DOWXRMYLEIDUDR-UHFFFAOYSA-N 5-fluoro-N-[5-[(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl]pyridin-2-yl]-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1CC2CCC(C1)N2C)C=1C=C2C(=NC=1)N=C(N2C(C)C)C DOWXRMYLEIDUDR-UHFFFAOYSA-N 0.000 description 1
VDUVGRFURLVFQC-UHFFFAOYSA-N 5-fluoro-N-[5-[(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl]pyridin-2-yl]-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1CC2CCC(C1)N2C)C1=CC=2C(N=C1)=NN(C=2C(C)C)C VDUVGRFURLVFQC-UHFFFAOYSA-N 0.000 description 1
ZNXVJYHKGLYXNQ-UHFFFAOYSA-N 5-fluoro-N-[5-[(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)sulfonyl]pyridin-2-yl]-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)S(=O)(=O)N1CC2CCC(C1)N2C)C=1C=C2C(=NC=1)N=C(N2C(C)C)C ZNXVJYHKGLYXNQ-UHFFFAOYSA-N 0.000 description 1
COYZXCDVMVJKCQ-UHFFFAOYSA-N 5-fluoro-N-[5-[(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)sulfonyl]pyridin-2-yl]-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)S(=O)(=O)N1CC2CCC(C1)N2C)C1=CC=2C(N=C1)=NN(C=2C(C)C)C COYZXCDVMVJKCQ-UHFFFAOYSA-N 0.000 description 1
HEKOJWHQLPOFJN-PMACEKPBSA-N 5-fluoro-N-[5-[[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]methyl]pyridin-2-yl]-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1[C@@H]2CN([C@H](C1)C2)C)C=1C=C2C(=NC=1)N=C(N2C(C)C)C HEKOJWHQLPOFJN-PMACEKPBSA-N 0.000 description 1
VWBWHIPJAAPDJH-GOSISDBHSA-N 5-fluoro-N-[5-[[(2R)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]methyl]pyridin-2-yl]-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1[C@@H](CN(CC1)C1COC1)C)C=1C=C2C(=NC=1)N=C(N2C(C)C)C VWBWHIPJAAPDJH-GOSISDBHSA-N 0.000 description 1
WMAYRLPSSAQOIE-GOSISDBHSA-N 5-fluoro-N-[5-[[(2R)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]methyl]pyridin-2-yl]-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1[C@@H](CN(CC1)C1COC1)C)C1=CC=2C(N=C1)=NN(C=2C(C)C)C WMAYRLPSSAQOIE-GOSISDBHSA-N 0.000 description 1
WMAYRLPSSAQOIE-SFHVURJKSA-N 5-fluoro-N-[5-[[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]methyl]pyridin-2-yl]-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1[C@H](CN(CC1)C1COC1)C)C1=CC=2C(N=C1)=NN(C=2C(C)C)C WMAYRLPSSAQOIE-SFHVURJKSA-N 0.000 description 1
YPTGIKFVDJSLSX-GOSISDBHSA-N 5-fluoro-N-[5-[[(3R)-3-methyl-4-(oxetan-3-yl)piperazin-1-yl]methyl]pyridin-2-yl]-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1C[C@H](N(CC1)C1COC1)C)C=1C=C2C(=NC=1)N=C(N2C(C)C)C YPTGIKFVDJSLSX-GOSISDBHSA-N 0.000 description 1
ACFOBWPAKSXGEZ-SFHVURJKSA-N 5-fluoro-N-[5-[[(3S)-3-methyl-4-(oxetan-3-yl)piperazin-1-yl]methyl]pyridin-2-yl]-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1C[C@@H](N(CC1)C1COC1)C)C1=CC=2C(N=C1)=NN(C=2C(C)C)C ACFOBWPAKSXGEZ-SFHVURJKSA-N 0.000 description 1
WEGQAYVHXXNNIF-UHFFFAOYSA-N 6-ethyl-N-[5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-yl]-7,8-dihydro-5H-1,6-naphthyridin-2-amine Chemical compound C(C)N1CC=2C=CC(=NC=2CC1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C)F WEGQAYVHXXNNIF-UHFFFAOYSA-N 0.000 description 1
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 1
ALGGPCBCKOVRKZ-UHFFFAOYSA-N 8-ethyl-3,8-diazabicyclo[3.2.1]octane Chemical compound C1NCC2CCC1N2CC ALGGPCBCKOVRKZ-UHFFFAOYSA-N 0.000 description 1
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
241000251468 Actinopterygii Species 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 1
KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical group NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
229940123877 Aurora kinase inhibitor Drugs 0.000 description 1
108091007065 BIRCs Proteins 0.000 description 1
108091032955 Bacterial small RNA Proteins 0.000 description 1
102100026596 Bcl-2-like protein 1 Human genes 0.000 description 1
235000021357 Behenic acid Nutrition 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
DPUOLQHDNGRHBS-UHFFFAOYSA-N Brassidinsaeure Natural products CCCCCCCCC=CCCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-UHFFFAOYSA-N 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
238000006443 Buchwald-Hartwig cross coupling reaction Methods 0.000 description 1
PATURKMKEJRUNW-UHFFFAOYSA-N C(C)(C)(C)N1C(=NC2=NC=C(C=C21)C2=NC(=NC=C2Cl)NC2=NC=C(C=C2)CN2CC=NC=C2)C Chemical compound C(C)(C)(C)N1C(=NC2=NC=C(C=C21)C2=NC(=NC=C2Cl)NC2=NC=C(C=C2)CN2CC=NC=C2)C PATURKMKEJRUNW-UHFFFAOYSA-N 0.000 description 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
241000283707 Capra Species 0.000 description 1
WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
241000700198 Cavia Species 0.000 description 1
229940123587 Cell cycle inhibitor Drugs 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
208000001333 Colorectal Neoplasms Diseases 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
102100032857 Cyclin-dependent kinase 1 Human genes 0.000 description 1
101710106279 Cyclin-dependent kinase 1 Proteins 0.000 description 1
102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 1
102100024457 Cyclin-dependent kinase 9 Human genes 0.000 description 1
ONIBWKKTOPOVIA-SCSAIBSYSA-N D-Proline Chemical compound OC(=O)[C@H]1CCCN1 ONIBWKKTOPOVIA-SCSAIBSYSA-N 0.000 description 1
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
229930182820 D-proline Natural products 0.000 description 1
102000009058 Death Domain Receptors Human genes 0.000 description 1
108010049207 Death Domain Receptors Proteins 0.000 description 1
201000004624 Dermatitis Diseases 0.000 description 1
206010012689 Diabetic retinopathy Diseases 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
208000002699 Digestive System Neoplasms Diseases 0.000 description 1
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
102100030013 Endoribonuclease Human genes 0.000 description 1
101710199605 Endoribonuclease Proteins 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
241001125671 Eretmochelys imbricata Species 0.000 description 1
URXZXNYJPAJJOQ-UHFFFAOYSA-N Erucic acid Natural products CCCCCCC=CCCCCCCCCCCCC(O)=O URXZXNYJPAJJOQ-UHFFFAOYSA-N 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 1
108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 1
GFYJLRABYLIFPC-UHFFFAOYSA-N FC=1C(=NC(=NC1)NC1=CC=C(C=N1)C=O)C=1C=C2C(=NC1)N=C(N2C(C)C)C Chemical compound FC=1C(=NC(=NC1)NC1=CC=C(C=N1)C=O)C=1C=C2C(=NC1)N=C(N2C(C)C)C GFYJLRABYLIFPC-UHFFFAOYSA-N 0.000 description 1
CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
208000032612 Glial tumor Diseases 0.000 description 1
206010018338 Glioma Diseases 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
208000009329 Graft vs Host Disease Diseases 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
102000003893 Histone acetyltransferases Human genes 0.000 description 1
108090000246 Histone acetyltransferases Proteins 0.000 description 1
108090000353 Histone deacetylase Proteins 0.000 description 1
102100038720 Histone deacetylase 9 Human genes 0.000 description 1
241001272567 Hominoidea Species 0.000 description 1
101000980930 Homo sapiens Cyclin-dependent kinase 9 Proteins 0.000 description 1
238000004566 IR spectroscopy Methods 0.000 description 1
JGZZHITWESAREC-UHFFFAOYSA-N Ic1ccc(CNCC2)c2n1 Chemical compound Ic1ccc(CNCC2)c2n1 JGZZHITWESAREC-UHFFFAOYSA-N 0.000 description 1
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 1
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
208000022559 Inflammatory bowel disease Diseases 0.000 description 1
102100024319 Intestinal-type alkaline phosphatase Human genes 0.000 description 1
241000713321 Intracisternal A-particles Species 0.000 description 1
LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
229940121730 Janus kinase 2 inhibitor Drugs 0.000 description 1
208000007766 Kaposi sarcoma Diseases 0.000 description 1
208000008839 Kidney Neoplasms Diseases 0.000 description 1
102000010638 Kinesin Human genes 0.000 description 1
108010063296 Kinesin Proteins 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
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 1
239000005639 Lauric acid Substances 0.000 description 1
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
239000012448 Lithium borohydride Substances 0.000 description 1
206010025323 Lymphomas Diseases 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
SRLUIDXAEQPJQZ-UHFFFAOYSA-N N-[4-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)-5-fluoropyrimidin-2-yl]-5,6,7,8-tetrahydro-1,6-naphthyridin-2-amine Chemical compound C(C)(C)(C)C=1N(N=C2N=CC(=CC2=1)C1=NC(=NC=C1F)NC1=NC=2CCNCC=2C=C1)C SRLUIDXAEQPJQZ-UHFFFAOYSA-N 0.000 description 1
ZDCKMDPDIVZCQN-UHFFFAOYSA-N N-[4-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)-5-fluoropyrimidin-2-yl]-6-methyl-7,8-dihydro-5H-1,6-naphthyridin-2-amine Chemical compound C(C)(C)(C)C=1N(N=C2N=CC(=CC2=1)C1=NC(=NC=C1F)NC1=NC=2CCN(CC=2C=C1)C)C ZDCKMDPDIVZCQN-UHFFFAOYSA-N 0.000 description 1
PKGAMDKFYPRURD-UHFFFAOYSA-N N-[5-(2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrol-5-ylmethyl)pyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1CC2CNCC2C1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C PKGAMDKFYPRURD-UHFFFAOYSA-N 0.000 description 1
OTBGCTYDRYXMLZ-UHFFFAOYSA-N N-[5-(2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrol-5-ylmethyl)pyridin-2-yl]-5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)CN1CC2CNCC2C1)C1=CC=2C(N=C1)=NN(C=2C(C)C)C OTBGCTYDRYXMLZ-UHFFFAOYSA-N 0.000 description 1
MKJWHEGWDHSUKW-UHFFFAOYSA-N N-[5-(2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrol-5-ylsulfonyl)pyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)S(=O)(=O)N1CC2CNCC2C1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C MKJWHEGWDHSUKW-UHFFFAOYSA-N 0.000 description 1
FRKDAHHJAVSESV-UHFFFAOYSA-N N-[5-(3,8-diazabicyclo[3.2.1]octan-3-ylmethyl)pyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound C12CN(CC(CC1)N2)CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C)F FRKDAHHJAVSESV-UHFFFAOYSA-N 0.000 description 1
QNASYWIEJBZBTH-UHFFFAOYSA-N N-[5-(3,8-diazabicyclo[3.2.1]octan-3-ylmethyl)pyridin-2-yl]-5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound C12CN(CC(CC1)N2)CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C1=CC=2C(N=C1)=NN(C=2C(C)C)C)F QNASYWIEJBZBTH-UHFFFAOYSA-N 0.000 description 1
VTBGFCFOXPCDNC-UHFFFAOYSA-N N-[5-(3,8-diazabicyclo[3.2.1]octan-3-ylsulfonyl)pyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound C12CN(CC(CC1)N2)S(=O)(=O)C=1C=CC(=NC=1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C)F VTBGFCFOXPCDNC-UHFFFAOYSA-N 0.000 description 1
HIUKIJAVMAMNRK-UHFFFAOYSA-N N-[5-(3,8-diazabicyclo[3.2.1]octan-3-ylsulfonyl)pyridin-2-yl]-5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound C12CN(CC(CC1)N2)S(=O)(=O)C=1C=CC(=NC=1)NC1=NC=C(C(=N1)C1=CC=2C(N=C1)=NN(C=2C(C)C)C)F HIUKIJAVMAMNRK-UHFFFAOYSA-N 0.000 description 1
GDYQWMGEUNBKHG-UHFFFAOYSA-N N-[5-(3,8-diazabicyclo[3.2.1]octan-8-ylmethyl)pyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound C12CNCC(CC1)N2CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C)F GDYQWMGEUNBKHG-UHFFFAOYSA-N 0.000 description 1
SVFUBMXEHZHPKF-UHFFFAOYSA-N N-[5-(3,8-diazabicyclo[3.2.1]octan-8-ylmethyl)pyridin-2-yl]-5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound C12CNCC(CC1)N2CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C1=CC=2C(N=C1)=NN(C=2C(C)C)C)F SVFUBMXEHZHPKF-UHFFFAOYSA-N 0.000 description 1
NYPBIQUVKPUVMJ-UHFFFAOYSA-N N-[5-(4-ethylpiperazin-1-yl)sulfonylpyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound C(C)N1CCN(CC1)S(=O)(=O)C=1C=CC(=NC=1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C)F NYPBIQUVKPUVMJ-UHFFFAOYSA-N 0.000 description 1
NSFRAHQIAILLSA-UHFFFAOYSA-N N-[5-[(2-ethyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)methyl]pyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound C(C)N1CC2C(C1)CN(C2)CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C)F NSFRAHQIAILLSA-UHFFFAOYSA-N 0.000 description 1
XTMMVHHPRCSAQQ-UHFFFAOYSA-N N-[5-[(2-ethyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)methyl]pyridin-2-yl]-5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound C(C)N1CC2C(C1)CN(C2)CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C1=CC=2C(N=C1)=NN(C=2C(C)C)C)F XTMMVHHPRCSAQQ-UHFFFAOYSA-N 0.000 description 1
JRLVHJNTMJUXPV-UHFFFAOYSA-N N-[5-[(2-ethyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)sulfonyl]pyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound C(C)N1CC2C(C1)CN(C2)S(=O)(=O)C=1C=CC(=NC=1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C)F JRLVHJNTMJUXPV-UHFFFAOYSA-N 0.000 description 1
UQNZITBETGUIJA-UHFFFAOYSA-N N-[5-[(2-ethyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)sulfonyl]pyridin-2-yl]-5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound C(C)N1CC2C(C1)CN(C2)S(=O)(=O)C=1C=CC(=NC=1)NC1=NC=C(C(=N1)C1=CC=2C(N=C1)=NN(C=2C(C)C)C)F UQNZITBETGUIJA-UHFFFAOYSA-N 0.000 description 1
SGAIWXGJMYYUCY-UHFFFAOYSA-N N-[5-[(3-ethyl-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl]pyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound C(C)N1CC2CCC(C1)N2CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C)F SGAIWXGJMYYUCY-UHFFFAOYSA-N 0.000 description 1
HQRCDDDJXIIDKH-UHFFFAOYSA-N N-[5-[(3-ethyl-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl]pyridin-2-yl]-5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound C(C)N1CC2CCC(C1)N2CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C1=CC=2C(N=C1)=NN(C=2C(C)C)C)F HQRCDDDJXIIDKH-UHFFFAOYSA-N 0.000 description 1
NTOMUIPJWWSMJA-UHFFFAOYSA-N N-[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]-5-fluoro-4-(1-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound C(C)N1CCN(CC1)CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N(N=C2C(C)C)C)F NTOMUIPJWWSMJA-UHFFFAOYSA-N 0.000 description 1
KKAQRYFELLGYJF-UHFFFAOYSA-N N-[5-[(8-ethyl-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl]pyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound C(C)N1C2CN(CC1CC2)CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C)F KKAQRYFELLGYJF-UHFFFAOYSA-N 0.000 description 1
SUPJWIISFGJSIP-UHFFFAOYSA-N N-[5-[(8-ethyl-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl]pyridin-2-yl]-5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-amine Chemical compound C(C)N1C2CN(CC1CC2)CC=1C=CC(=NC=1)NC1=NC=C(C(=N1)C1=CC=2C(N=C1)=NN(C=2C(C)C)C)F SUPJWIISFGJSIP-UHFFFAOYSA-N 0.000 description 1
OHQTVVOGIIRXNP-UHFFFAOYSA-N N-[5-[(8-ethyl-3,8-diazabicyclo[3.2.1]octan-3-yl)sulfonyl]pyridin-2-yl]-5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-amine Chemical compound C(C)N1C2CN(CC1CC2)S(=O)(=O)C=1C=CC(=NC=1)NC1=NC=C(C(=N1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C)F OHQTVVOGIIRXNP-UHFFFAOYSA-N 0.000 description 1
CKERNBMDYQJBJT-HXUWFJFHSA-N N-[5-[[(8aR)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]methyl]pyridin-2-yl]-4-(3-tert-butyl-2-methylpyrazolo[3,4-b]pyridin-5-yl)-5-fluoropyrimidin-2-amine Chemical compound C(C)(C)(C)C=1N(N=C2N=CC(=CC2=1)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1C[C@@H]2N(CC1)CCC2)C CKERNBMDYQJBJT-HXUWFJFHSA-N 0.000 description 1
YUVAXBUOGGOKTC-UHFFFAOYSA-N N-[5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-yl]-5,6,7,8-tetrahydro-1,6-naphthyridin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=2CCNCC=2C=C1)C=1C=C2C(=NC=1)N=C(N2C(C)C)C YUVAXBUOGGOKTC-UHFFFAOYSA-N 0.000 description 1
BWOFAGGSBDGUBK-UHFFFAOYSA-N N-[5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-yl]-6-methyl-7,8-dihydro-5H-1,6-naphthyridin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=2CCN(CC=2C=C1)C)C=1C=C2C(=NC=1)N=C(N2C(C)C)C BWOFAGGSBDGUBK-UHFFFAOYSA-N 0.000 description 1
UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
206010028813 Nausea Diseases 0.000 description 1
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
MBKMCBQLIZVKGG-KZUDCZAMSA-N OC(N1[C@@H](CC2=CC=CC=C2)C(CCC2)N2CC1)=O Chemical compound OC(N1[C@@H](CC2=CC=CC=C2)C(CCC2)N2CC1)=O MBKMCBQLIZVKGG-KZUDCZAMSA-N 0.000 description 1
239000005642 Oleic acid Substances 0.000 description 1
108700020796 Oncogene Proteins 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
240000007594 Oryza sativa Species 0.000 description 1
235000007164 Oryza sativa Nutrition 0.000 description 1
206010033128 Ovarian cancer Diseases 0.000 description 1
235000021314 Palmitic acid Nutrition 0.000 description 1
241000282579 Pan Species 0.000 description 1
206010033645 Pancreatitis Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
206010060862 Prostate cancer Diseases 0.000 description 1
208000000236 Prostatic Neoplasms Diseases 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
241000700159 Rattus Species 0.000 description 1
229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 1
206010063837 Reperfusion injury Diseases 0.000 description 1
206010038933 Retinopathy of prematurity Diseases 0.000 description 1
206010039710 Scleroderma Diseases 0.000 description 1
206010040070 Septic Shock Diseases 0.000 description 1
101710113029 Serine/threonine-protein kinase Proteins 0.000 description 1
229910004298 SiO 2 Inorganic materials 0.000 description 1
108020004459 Small interfering RNA Proteins 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
241000282887 Suidae Species 0.000 description 1
238000006069 Suzuki reaction reaction Methods 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
206010052779 Transplant rejections Diseases 0.000 description 1
235000021307 Triticum Nutrition 0.000 description 1
244000098338 Triticum aestivum Species 0.000 description 1
YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
229940127507 Ubiquitin Ligase Inhibitors Drugs 0.000 description 1
208000036142 Viral infection Diseases 0.000 description 1
241000700605 Viruses Species 0.000 description 1
229930003427 Vitamin E Natural products 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
SMEGJBVQLJJKKX-HOTMZDKISA-N [(2R,3S,4S,5R,6R)-5-acetyloxy-3,4,6-trihydroxyoxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@@H](O1)O)OC(=O)C)O)O SMEGJBVQLJJKKX-HOTMZDKISA-N 0.000 description 1
JAWMENYCRQKKJY-UHFFFAOYSA-N [3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-ylmethyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl]-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]methanone Chemical compound N1N=NC=2CN(CCC=21)CC1=NOC2(C1)CCN(CC2)C(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F JAWMENYCRQKKJY-UHFFFAOYSA-N 0.000 description 1
MIAHFULQHQHVKY-UHFFFAOYSA-N [6-[[5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-yl]amino]pyridin-3-yl]-(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)methanone Chemical compound FC=1C(=NC(=NC=1)NC1=CC=C(C=N1)C(=O)N1CC2CN(CC2C1)C)C=1C=C2C(=NC=1)N=C(N2C(C)C)C MIAHFULQHQHVKY-UHFFFAOYSA-N 0.000 description 1
SHSPUWCKPBMEPG-UHFFFAOYSA-N [6-[[5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-yl]amino]pyridin-3-yl]-(4-methylpiperazin-1-yl)methanone Chemical compound FC=1C(=NC(=NC=1)NC1=CC=C(C=N1)C(=O)N1CCN(CC1)C)C=1C=C2C(=NC=1)N=C(N2C(C)C)C SHSPUWCKPBMEPG-UHFFFAOYSA-N 0.000 description 1
NTUNQVNRPCWODX-UHFFFAOYSA-N [6-[[5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-yl]amino]pyridin-3-yl]-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)methanone Chemical compound FC=1C(=NC(=NC=1)NC1=CC=C(C=N1)C(=O)N1CC2CCC(C1)N2C)C=1C=C2C(=NC=1)N=C(N2C(C)C)C NTUNQVNRPCWODX-UHFFFAOYSA-N 0.000 description 1
OIXJJHPWGOLKOI-UHFFFAOYSA-N [6-[[5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-yl]amino]pyridin-3-yl]-(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)methanone Chemical compound FC=1C(=NC(=NC=1)NC1=CC=C(C=N1)C(=O)N1CC2CN(CC2C1)C)C1=CC=2C(N=C1)=NN(C=2C(C)C)C OIXJJHPWGOLKOI-UHFFFAOYSA-N 0.000 description 1
GCVGXNPYADFONH-UHFFFAOYSA-N [6-[[5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-yl]amino]pyridin-3-yl]-(3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone Chemical compound FC=1C(=NC(=NC=1)NC1=CC=C(C=N1)C(=O)N1C2CN(CC1CC2)C)C1=CC=2C(N=C1)=NN(C=2C(C)C)C GCVGXNPYADFONH-UHFFFAOYSA-N 0.000 description 1
LLVXWLYIXHSNFK-UHFFFAOYSA-N [6-[[5-fluoro-4-(2-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-5-yl)pyrimidin-2-yl]amino]pyridin-3-yl]-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)methanone Chemical compound FC=1C(=NC(=NC=1)NC1=CC=C(C=N1)C(=O)N1CC2CCC(C1)N2C)C1=CC=2C(N=C1)=NN(C=2C(C)C)C LLVXWLYIXHSNFK-UHFFFAOYSA-N 0.000 description 1
KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
229940081735 acetylcellulose Drugs 0.000 description 1
230000009471 action Effects 0.000 description 1
239000012190 activator Substances 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
206010064930 age-related macular degeneration Diseases 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
238000006136 alcoholysis reaction Methods 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
229930013930 alkaloid Natural products 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
150000003927 aminopyridines Chemical class 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000004037 angiogenesis inhibitor Substances 0.000 description 1
229940121369 angiogenesis inhibitor Drugs 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
238000010171 animal model Methods 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
229940124650 anti-cancer therapies Drugs 0.000 description 1
230000000340 anti-metabolite Effects 0.000 description 1
230000002927 anti-mitotic effect Effects 0.000 description 1
230000001062 anti-nausea Effects 0.000 description 1
230000001028 anti-proliverative effect Effects 0.000 description 1
230000000840 anti-viral effect Effects 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
239000000611 antibody drug conjugate Substances 0.000 description 1
229940049595 antibody-drug conjugate Drugs 0.000 description 1
238000011319 anticancer therapy Methods 0.000 description 1
229940100197 antimetabolite Drugs 0.000 description 1
239000002256 antimetabolite Substances 0.000 description 1
230000001640 apoptogenic effect Effects 0.000 description 1
230000006907 apoptotic process Effects 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
239000003719 aurora kinase inhibitor Substances 0.000 description 1
HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
229940116226 behenic acid Drugs 0.000 description 1
150000001555 benzenes Chemical class 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
229960003237 betaine Drugs 0.000 description 1
GPRLTFBKWDERLU-UHFFFAOYSA-N bicyclo[2.2.2]octane Chemical group C1CC2CCC1CC2 GPRLTFBKWDERLU-UHFFFAOYSA-N 0.000 description 1
SHOMMGQAMRXRRK-UHFFFAOYSA-N bicyclo[3.1.1]heptane Chemical group C1C2CC1CCC2 SHOMMGQAMRXRRK-UHFFFAOYSA-N 0.000 description 1
GNTFBMAGLFYMMZ-UHFFFAOYSA-N bicyclo[3.2.2]nonane Chemical group C1CC2CCC1CCC2 GNTFBMAGLFYMMZ-UHFFFAOYSA-N 0.000 description 1
WNTGVOIBBXFMLR-UHFFFAOYSA-N bicyclo[3.3.1]nonane Chemical group C1CCC2CCCC1C2 WNTGVOIBBXFMLR-UHFFFAOYSA-N 0.000 description 1
KVLCIHRZDOKRLK-UHFFFAOYSA-N bicyclo[4.2.1]nonane Chemical group C1C2CCC1CCCC2 KVLCIHRZDOKRLK-UHFFFAOYSA-N 0.000 description 1
102000023732 binding proteins Human genes 0.000 description 1
108091008324 binding proteins Proteins 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
210000003969 blast cell Anatomy 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000001124 body fluid Anatomy 0.000 description 1
239000010839 body fluid Substances 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
239000012267 brine Substances 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
239000000872 buffer Substances 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
229960001948 caffeine Drugs 0.000 description 1
VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
235000013539 calcium stearate Nutrition 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
208000035269 cancer or benign tumor Diseases 0.000 description 1
230000000711 cancerogenic effect Effects 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
231100000315 carcinogenic Toxicity 0.000 description 1
239000004359 castor oil Substances 0.000 description 1
235000019438 castor oil Nutrition 0.000 description 1
230000006369 cell cycle progression Effects 0.000 description 1
230000010261 cell growth Effects 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002301 cellulose acetate Polymers 0.000 description 1
230000008859 change Effects 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
238000013329 compounding Methods 0.000 description 1
238000007906 compression Methods 0.000 description 1
230000006835 compression Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
239000006071 cream Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
239000002875 cyclin dependent kinase inhibitor Substances 0.000 description 1
125000001316 cycloalkyl alkyl group Chemical group 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
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
238000013461 design Methods 0.000 description 1
239000003599 detergent Substances 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 1
208000037765 diseases and disorders Diseases 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
238000004980 dosimetry Methods 0.000 description 1
238000000132 electrospray ionisation Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
239000002532 enzyme inhibitor Substances 0.000 description 1
210000002615 epidermis Anatomy 0.000 description 1
DPUOLQHDNGRHBS-KTKRTIGZSA-N erucic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-KTKRTIGZSA-N 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
TUCBIILSAIXHOQ-UHFFFAOYSA-N ethyl 2-aminoacetate;2,2,2-trifluoroacetic acid Chemical compound CCOC(=O)CN.OC(=O)C(F)(F)F TUCBIILSAIXHOQ-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
239000010685 fatty oil Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 1
IRXSLJNXXZKURP-UHFFFAOYSA-N fluorenylmethyloxycarbonyl chloride Chemical compound C1=CC=C2C(COC(=O)Cl)C3=CC=CC=C3C2=C1 IRXSLJNXXZKURP-UHFFFAOYSA-N 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
239000000499 gel Substances 0.000 description 1
108091006104 gene-regulatory proteins Proteins 0.000 description 1
102000034356 gene-regulatory proteins Human genes 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
208000024908 graft versus host disease Diseases 0.000 description 1
230000012010 growth Effects 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
210000003128 head Anatomy 0.000 description 1
230000036541 health Effects 0.000 description 1
201000011066 hemangioma Diseases 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004446 heteroarylalkyl group Chemical group 0.000 description 1
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 description 1
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
229960002885 histidine Drugs 0.000 description 1
238000001794 hormone therapy Methods 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
KJDJPXUIZYHXEZ-UHFFFAOYSA-N hydrogen sulfate;methylaminoazanium Chemical compound CN[NH3+].OS([O-])(=O)=O KJDJPXUIZYHXEZ-UHFFFAOYSA-N 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
206010020718 hyperplasia Diseases 0.000 description 1
230000003463 hyperproliferative effect Effects 0.000 description 1
208000026278 immune system disease Diseases 0.000 description 1
230000036039 immunity Effects 0.000 description 1
239000000367 immunologic factor Substances 0.000 description 1
238000002513 implantation Methods 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
239000003978 infusion fluid Substances 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
238000011081 inoculation Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
YAQXGBBDJYBXKL-UHFFFAOYSA-N iron(2+);1,10-phenanthroline;dicyanide Chemical compound [Fe+2].N#[C-].N#[C-].C1=CN=C2C3=NC=CC=C3C=CC2=C1.C1=CN=C2C3=NC=CC=C3C=CC2=C1 YAQXGBBDJYBXKL-UHFFFAOYSA-N 0.000 description 1
229940045996 isethionic acid Drugs 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 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
XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
230000000155 isotopic effect Effects 0.000 description 1
238000001948 isotopic labelling Methods 0.000 description 1
GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
210000002510 keratinocyte Anatomy 0.000 description 1
208000017169 kidney disease Diseases 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000008101 lactose Substances 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
150000004668 long chain fatty acids Chemical class 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
208000037841 lung tumor Diseases 0.000 description 1
208000002780 macular degeneration Diseases 0.000 description 1
CQRPUKWAZPZXTO-UHFFFAOYSA-M magnesium;2-methylpropane;chloride Chemical compound [Mg+2].[Cl-].C[C-](C)C CQRPUKWAZPZXTO-UHFFFAOYSA-M 0.000 description 1
230000014759 maintenance of location Effects 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
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
229940099690 malic acid Drugs 0.000 description 1
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
210000004962 mammalian cell Anatomy 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
239000000463 material Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
239000002609 medium Substances 0.000 description 1
230000037353 metabolic pathway Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
229960002900 methylcellulose Drugs 0.000 description 1
230000003641 microbiacidal effect Effects 0.000 description 1
229940124561 microbicide Drugs 0.000 description 1
239000003226 mitogen Substances 0.000 description 1
230000005404 monopole Effects 0.000 description 1
125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 1
125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
HWWVAHCWJLGKLW-UHFFFAOYSA-N n,n-dimethylhydroxylamine;hydron;chloride Chemical compound Cl.CN(C)O HWWVAHCWJLGKLW-UHFFFAOYSA-N 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
125000004957 naphthylene group Chemical group 0.000 description 1
125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
230000008693 nausea Effects 0.000 description 1
210000003739 neck Anatomy 0.000 description 1
230000004770 neurodegeneration Effects 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
208000014500 neuronal tumor Diseases 0.000 description 1
230000011242 neutrophil chemotaxis Effects 0.000 description 1
FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical group C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000003791 organic solvent mixture Substances 0.000 description 1
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
201000008968 osteosarcoma Diseases 0.000 description 1
230000002611 ovarian Effects 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
208000008443 pancreatic carcinoma Diseases 0.000 description 1
239000011713 pantothenic acid Substances 0.000 description 1
229940055726 pantothenic acid Drugs 0.000 description 1
235000019161 pantothenic acid Nutrition 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 1
XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
238000000554 physical therapy Methods 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
239000000049 pigment Substances 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229920000768 polyamine Polymers 0.000 description 1
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
229940116317 potato starch Drugs 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000008569 process Effects 0.000 description 1
238000012545 processing Methods 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
208000023958 prostate neoplasm Diseases 0.000 description 1
229940121649 protein inhibitor Drugs 0.000 description 1
239000012268 protein inhibitor Substances 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
238000001671 psychotherapy Methods 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
150000003212 purines Chemical class 0.000 description 1
125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 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
ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical compound NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
150000003230 pyrimidines Chemical class 0.000 description 1
NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
RONWGALEIBILOG-VMJVVOMYSA-N quinine sulfate Chemical compound [H+].[H+].[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 RONWGALEIBILOG-VMJVVOMYSA-N 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
238000001959 radiotherapy Methods 0.000 description 1
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 description 1
108091006082 receptor inhibitors Proteins 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
208000037803 restenosis Diseases 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
235000009566 rice Nutrition 0.000 description 1
229940100486 rice starch Drugs 0.000 description 1
229920002477 rna polymer Polymers 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
230000011218 segmentation Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000036303 septic shock Effects 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
208000015891 sexual disease Diseases 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
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 description 1
229960002930 sirolimus Drugs 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
208000017520 skin disease Diseases 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000017550 sodium carbonate Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
239000007901 soft capsule 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
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
125000003003 spiro group Chemical group 0.000 description 1
208000012972 squamous cell carcinoma of colon Diseases 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
125000005017 substituted alkenyl group Chemical group 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
125000004426 substituted alkynyl group Chemical group 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
201000000596 systemic lupus erythematosus Diseases 0.000 description 1
238000009492 tablet coating Methods 0.000 description 1
239000002700 tablet coating Substances 0.000 description 1
238000002626 targeted therapy Methods 0.000 description 1
230000008685 targeting Effects 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
GZVYQUVSTREGTR-VXKWHMMOSA-N tert-butyl (1S,4S)-5-[[6-[[5-fluoro-4-(2-methyl-1-propan-2-ylimidazo[4,5-b]pyridin-6-yl)pyrimidin-2-yl]amino]pyridin-3-yl]methyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical group FC=1C(=NC(=NC=1)NC1=CC=C(C=N1)CN1[C@@H]2CN([C@H](C1)C2)C(=O)OC(C)(C)C)C=1C=C2C(=NC=1)N=C(N2C(C)C)C GZVYQUVSTREGTR-VXKWHMMOSA-N 0.000 description 1
UXAWXZDXVOYLII-YUMQZZPRSA-N tert-butyl (1s,4s)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1[C@@H]2N(C(=O)OC(C)(C)C)C[C@H]1NC2 UXAWXZDXVOYLII-YUMQZZPRSA-N 0.000 description 1
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000005934 tert-pentyloxycarbonyl group Chemical group 0.000 description 1
238000010998 test method Methods 0.000 description 1
230000002381 testicular Effects 0.000 description 1
238000012360 testing method Methods 0.000 description 1
TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
229960004559 theobromine Drugs 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
201000002510 thyroid cancer Diseases 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
208000013076 thyroid tumor Diseases 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
229940078499 tricalcium phosphate Drugs 0.000 description 1
235000019731 tricalcium phosphate Nutrition 0.000 description 1
229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
PCFIPYFVXDCWBW-UHFFFAOYSA-N tricyclo[3.3.1.03,7]nonane Chemical group C1C(C2)C3CC2CC1C3 PCFIPYFVXDCWBW-UHFFFAOYSA-N 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229910052722 tritium Inorganic materials 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
230000005747 tumor angiogenesis Effects 0.000 description 1
208000025421 tumor of uterus Diseases 0.000 description 1
238000000870 ultraviolet spectroscopy Methods 0.000 description 1
231100000402 unacceptable toxicity Toxicity 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
206010046766 uterine cancer Diseases 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
235000019165 vitamin E Nutrition 0.000 description 1
229940046009 vitamin E Drugs 0.000 description 1
239000011709 vitamin E Substances 0.000 description 1
239000003643 water by type Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
229940100445 wheat starch Drugs 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
- 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
- C07D487/08—Bridged systems
- 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
- C07D487/10—Spiro-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyridine Compounds (AREA)

TW106103864A 2016-02-06 2017-02-06 6-5元稠合唑環衍生物及其藥物組合物，以及作為藥物的應用 TWI736578B (zh)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US201662292259P	2016-02-06	2016-02-06
US62/292,259		2016-02-06

Publications (2)

Publication Number	Publication Date
TW201801729A TW201801729A (zh)	2018-01-16
TWI736578B true TWI736578B (zh)	2021-08-21

Family

ID=59500239

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
TW106103864A TWI736578B (zh)	2016-02-06	2017-02-06	6-5元稠合唑環衍生物及其藥物組合物，以及作為藥物的應用

Country Status (3)

Country	Link
CN (1)	CN108602799B (fr)
TW (1)	TWI736578B (fr)
WO (1)	WO2017133701A1 (fr)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN107337634B (zh) *	2017-08-28	2019-07-09	新发药业有限公司	一种阿贝西利中间体化合物的制备方法
JP2021514359A (ja)	2018-02-15	2021-06-10	ニューベイション・バイオ・インコーポレイテッドＮｕｖａｔｉｏｎＢｉｏＩｎｃ．	キナーゼ阻害剤としての複素環式化合物
GEP20227433B (en)	2018-04-26	2022-10-25	Pfizer	2-amino-pyridine or 2-amino-pyrimidine derivatives as cyclin dependent kinase inhibitors
MX2021000895A (es)	2018-07-27	2021-08-24	California Inst Of Techn	Inhibidores de cinasas dependientes de ciclinas (cdk) y usos de los mismos.
MA55909A (fr) *	2019-05-05	2022-03-16	Qilu Regor Therapeutics Inc	Inhibiteurs de cdk
CN111303128B (zh) *	2020-04-07	2020-10-27	苏州信诺维医药科技有限公司	一种多环类化合物、其制备方法及应用
US11685744B2 (en)	2020-09-21	2023-06-27	Prelude Therapeutics Incorporated	CDK inhibitors and their use as pharmaceuticals
WO2022113003A1 (fr)	2020-11-27	2022-06-02	Rhizen Pharmaceuticals Ag	Inhibiteurs de cdk
WO2022149057A1 (fr)	2021-01-05	2022-07-14	Rhizen Pharmaceuticals Ag	Inhibiteurs de cdk
CA3245813A1 (fr) *	2022-03-23	2023-09-28	Prelude Therapeutics, Incorporated	Composés polymorphes et leurs utilisations
KR20250002427A (ko) *	2022-04-08	2025-01-07	바이오렉시스 테라퓨틱스, 인크.	Cdk9 억제제

Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN102264725A (zh) *	2008-12-22	2011-11-30	伊莱利利公司	蛋白激酶抑制剂
WO2016014904A1 (fr) *	2014-07-24	2016-01-28	Beta Pharma, Inc.	Dérivés de 2-h-indazole en tant qu'inhibiteurs de la kinase dépendante de la cycline (cdk) et leurs utilisations thérapeutiques

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2654670A1 (fr) *	2006-07-06	2008-01-10	Boehringer Ingelheim International Gmbh	Nouveaux composes
US9796701B2 (en) *	2013-12-31	2017-10-24	Xuanzhu Pharma Co., Ltd.	Kinase inhibitor and use thereof
WO2016015605A1 (fr) *	2014-07-26	2016-02-04	Sunshine Lake Pharma Co., Ltd.	Composés en tant que petites molécules inhibitrices de la cdk et leurs utilisations
CN105732615B (zh) *	2014-12-31	2018-05-01	山东轩竹医药科技有限公司	Cdk激酶抑制剂
CN105111191B (zh) *	2015-07-21	2018-06-08	上海皓元生物医药科技有限公司	一种用于合成cdk9抑制剂的关键中间体及其制备方法和用途

2017
- 2017-02-06 WO PCT/CN2017/072958 patent/WO2017133701A1/fr not_active Ceased
- 2017-02-06 CN CN201780010075.XA patent/CN108602799B/zh not_active Expired - Fee Related
- 2017-02-06 TW TW106103864A patent/TWI736578B/zh not_active IP Right Cessation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN102264725A (zh) *	2008-12-22	2011-11-30	伊莱利利公司	蛋白激酶抑制剂
WO2016014904A1 (fr) *	2014-07-24	2016-01-28	Beta Pharma, Inc.	Dérivés de 2-h-indazole en tant qu'inhibiteurs de la kinase dépendante de la cycline (cdk) et leurs utilisations thérapeutiques

Also Published As

Publication number	Publication date
WO2017133701A1 (fr)	2017-08-10
CN108602799A (zh)	2018-09-28
CN108602799B (zh)	2021-08-03
TW201801729A (zh)	2018-01-16

Legal Events

Date	Code	Title	Description
2024-05-21	MM4A	Annulment or lapse of patent due to non-payment of fees

Publication	Publication Date	Title
TWI736578B (zh)	2021-08-21	6-5元稠合唑環衍生物及其藥物組合物，以及作為藥物的應用
JP7535537B2 (ja)	2024-08-16	タンパク質キナーゼ阻害剤としての置換ピロロ［２，３－ｂ］ピリジン及びピラゾロ［３，４－ｂ］ピリジン誘導体
EP3765462B1 (fr)	2023-10-18	Composés de (2-azabicyclo [3.1.0] hexan-2-yl) pyrazolo [1, 5-a] pyrimidine et imidazo [1, 2-b] pyridazine substitués en tant qu'inhibiteurs de kinases trk
CN115551856A (zh)	2022-12-30	作为cdk2/4/6抑制剂的化合物
CN111971287A (zh)	2020-11-20	作为trk激酶抑制剂的大环化合物
TW202144357A (zh)	2021-12-01	作為激酶抑制劑的化合物
TW202028209A (zh)	2020-08-01	作為RET激酶抑制劑的取代的咪唑[1,2-a]吡啶和[1,2,4]三唑[1,5-a]吡啶化合物
JP6927548B2 (ja)	2021-09-01	ある種のタンパク質キナーゼ阻害剤
WO2021047584A1 (fr)	2021-03-18	Composés de (2-azabicyclo [3.1.0] hexan-2-yl) pyrazolo [1, 5-a] pyrimidine et imidazo [1, 2-b] pyridazine substitués utilisés comme inhibiteurs de kinases trk
TWI791444B (zh)	2023-02-11	作為激酶抑制劑的取代的吡咯并[2,3-d]噠嗪-4-酮和吡唑并[3,4-d]噠嗪-4-酮
JP2023549273A (ja)	2023-11-22	プロテインキナ－ゼ阻害剤としての置換されたピロロ［２，３－ｂ］ピリジン及びピラゾロ［３，４－ｂ］ピリジン誘導体
TW202017927A (zh)	2020-05-16	作爲RET激酶抑制劑的取代的[1,2,4]三唑[1,5-a]吡啶化合物
TWI827869B (zh)	2024-01-01	作為蛋白激酶抑制劑的取代的吡咯並[2,3-b]吡啶及吡唑並[3,4-b]吡啶衍生物
RU2778294C2 (ru)	2022-08-17	Макроциклические соединения как ингибиторы киназ trk
TW202028199A (zh)	2020-08-01	作為蛋白激酶抑制劑的萘啶酮和吡啶基嘧啶酮類化合物
CN115605481A (zh)	2023-01-13	作为激酶抑制剂的化合物
HK40034411A (en)	2021-04-23	Substituted (2-azabicyclo [3.1.0] hexan-2-yl) pyrazolo [1, 5-a] pyrimidine and imidazo [1, 2-b] pyridazine compounds as trk kinases inhibitors
HK40034417A (en)	2021-04-23	Macrocyclic compounds as trk kinases inhibitors