TWI673268B - 作為ｆｇｆｒ４抑制劑之稠環雙環吡啶基衍生物 - Google Patents

作為ｆｇｆｒ４抑制劑之稠環雙環吡啶基衍生物 Download PDF

Info

Publication number: TWI673268B
Authority: TW; Taiwan
Prior art keywords: formamidine; pyridin; dihydro; cyano; hydroxymethyl
Prior art date: 2013-10-25

Application number

TW103136873A

Other languages

English (en)

Chinese (zh)

Other versions

TW201605853A (zh

Inventor

尼可布舒曼

羅賓艾拉克菲哈斯特

派斯可佛瑞特

湯瑪士克努普芙

凱薩琳萊柏蘭克

廖律

勞伯特馬

皮耶尼姆斯葛恩

賽巴斯汀瑞普許

熊淨

Original Assignee

瑞士商諾華公司

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.)

2013-10-25

Filing date

2014-10-24

Publication date

2019-10-01

2014-10-24 Application filed by 瑞士商諾華公司 filed Critical 瑞士商諾華公司

2016-02-16 Publication of TW201605853A publication Critical patent/TW201605853A/zh

2019-10-01 Application granted granted Critical

2019-10-01 Publication of TWI673268B publication Critical patent/TWI673268B/zh

Links

239000003112 inhibitor Substances 0.000 title description 36
101150082429 FGFR4 gene Proteins 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 388
150000003839 salts Chemical class 0.000 claims abstract description 121
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 22
239000013543 active substance Substances 0.000 claims abstract description 5
238000004519 manufacturing process Methods 0.000 claims abstract description 5
-1 C 1 -C 6 alkyl Chemical group 0.000 claims description 508
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 107
229920006395 saturated elastomer Polymers 0.000 claims description 96
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 44
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 41
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 36
239000003814 drug Substances 0.000 claims description 30
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
229910052760 oxygen Inorganic materials 0.000 claims description 28
229910052739 hydrogen Inorganic materials 0.000 claims description 25
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
125000005843 halogen group Chemical group 0.000 claims description 23
125000005842 heteroatom Chemical group 0.000 claims description 23
239000001257 hydrogen Substances 0.000 claims description 22
206010028980 Neoplasm Diseases 0.000 claims description 21
201000011510 cancer Diseases 0.000 claims description 20
201000007270 liver cancer Diseases 0.000 claims description 20
208000014018 liver neoplasm Diseases 0.000 claims description 20
150000001408 amides Chemical class 0.000 claims description 19
229910052799 carbon Inorganic materials 0.000 claims description 19
229910052736 halogen Inorganic materials 0.000 claims description 15
150000002367 halogens Chemical group 0.000 claims description 15
229910052717 sulfur Inorganic materials 0.000 claims description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 14
150000002431 hydrogen Chemical group 0.000 claims description 14
125000000623 heterocyclic group Chemical group 0.000 claims description 13
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 12
CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 8
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 7
229910052757 nitrogen Inorganic materials 0.000 claims description 7
125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
206010006187 Breast cancer Diseases 0.000 claims description 6
208000026310 Breast neoplasm Diseases 0.000 claims description 6
206010009944 Colon cancer Diseases 0.000 claims description 6
208000005718 Stomach Neoplasms Diseases 0.000 claims description 6
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 6
208000029742 colonic neoplasm Diseases 0.000 claims description 6
125000004093 cyano group Chemical group *C#N 0.000 claims description 6
206010017758 gastric cancer Diseases 0.000 claims description 6
125000001475 halogen functional group Chemical group 0.000 claims description 6
201000011549 stomach cancer Diseases 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
206010058467 Lung neoplasm malignant Diseases 0.000 claims description 5
206010033128 Ovarian cancer Diseases 0.000 claims description 5
206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
206010060862 Prostate cancer Diseases 0.000 claims description 5
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
208000005017 glioblastoma Diseases 0.000 claims description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
201000005202 lung cancer Diseases 0.000 claims description 5
208000020816 lung neoplasm Diseases 0.000 claims description 5
201000009410 rhabdomyosarcoma Diseases 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 3
125000004430 oxygen atom Chemical group O* 0.000 claims description 3
229940095064 tartrate Drugs 0.000 claims description 3
WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims description 2
125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 2
229910052727 yttrium Inorganic materials 0.000 claims description 2
150000001860 citric acid derivatives Chemical class 0.000 claims 2
125000004122 cyclic group Chemical group 0.000 claims 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 claims 1
125000001072 heteroaryl group Chemical group 0.000 claims 1
125000004434 sulfur atom Chemical group 0.000 claims 1
238000000034 method Methods 0.000 abstract description 33
230000001225 therapeutic effect Effects 0.000 abstract description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 262
239000000243 solution Substances 0.000 description 174
239000011541 reaction mixture Substances 0.000 description 173
239000000543 intermediate Substances 0.000 description 165
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 136
235000019439 ethyl acetate Nutrition 0.000 description 130
239000011734 sodium Substances 0.000 description 125
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 124
238000001946 ultra-performance liquid chromatography-mass spectrometry Methods 0.000 description 124
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 119
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 116
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 100
239000000203 mixture Substances 0.000 description 94
239000007787 solid Substances 0.000 description 90
239000013067 intermediate product Substances 0.000 description 85
239000012044 organic layer Substances 0.000 description 83
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 81
239000012071 phase Substances 0.000 description 81
238000004587 chromatography analysis Methods 0.000 description 80
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 80
239000013058 crude material Substances 0.000 description 77
239000007864 aqueous solution Substances 0.000 description 63
238000005481 NMR spectroscopy Methods 0.000 description 52
102100027844 Fibroblast growth factor receptor 4 Human genes 0.000 description 50
101000917134 Homo sapiens Fibroblast growth factor receptor 4 Proteins 0.000 description 48
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 47
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 44
239000000460 chlorine Substances 0.000 description 42
239000000377 silicon dioxide Substances 0.000 description 42
239000000741 silica gel Substances 0.000 description 39
229910002027 silica gel Inorganic materials 0.000 description 39
239000012267 brine Substances 0.000 description 37
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 37
239000000047 product Substances 0.000 description 37
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 37
230000002829 reductive effect Effects 0.000 description 36
IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 34
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 32
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 32
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 32
201000010099 disease Diseases 0.000 description 31
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 30
238000006243 chemical reaction Methods 0.000 description 29
239000012074 organic phase Substances 0.000 description 29
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 23
238000003756 stirring Methods 0.000 description 23
229940124597 therapeutic agent Drugs 0.000 description 23
229910052720 vanadium Inorganic materials 0.000 description 23
239000003643 water by type Substances 0.000 description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
238000004808 supercritical fluid chromatography Methods 0.000 description 21
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 20
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 19
239000000725 suspension Substances 0.000 description 18
229910052805 deuterium Inorganic materials 0.000 description 17
238000004458 analytical method Methods 0.000 description 16
229910052786 argon Inorganic materials 0.000 description 16
239000003153 chemical reaction reagent Substances 0.000 description 16
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 15
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 15
235000019253 formic acid Nutrition 0.000 description 15
GBKZCKNJGIKMGP-UHFFFAOYSA-N 6-amino-4-fluoropyridine-3-carbonitrile Chemical compound Nc1cc(F)c(cn1)C#N GBKZCKNJGIKMGP-UHFFFAOYSA-N 0.000 description 14
239000002253 acid Substances 0.000 description 14
125000000217 alkyl group Chemical group 0.000 description 14
239000003795 chemical substances by application Substances 0.000 description 14
230000000694 effects Effects 0.000 description 13
239000010410 layer Substances 0.000 description 13
239000003921 oil Substances 0.000 description 13
235000019198 oils Nutrition 0.000 description 13
239000000843 powder Substances 0.000 description 13
238000004366 reverse phase liquid chromatography Methods 0.000 description 13
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
108091000080 Phosphotransferase Proteins 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
210000004027 cell Anatomy 0.000 description 12
230000001404 mediated effect Effects 0.000 description 12
102000020233 phosphotransferase Human genes 0.000 description 12
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 11
239000002904 solvent Substances 0.000 description 11
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
239000004480 active ingredient Substances 0.000 description 10
239000013078 crystal Substances 0.000 description 10
229920001296 polysiloxane Polymers 0.000 description 10
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
150000001412 amines Chemical class 0.000 description 9
150000001721 carbon Chemical group 0.000 description 9
239000012948 isocyanate Substances 0.000 description 9
108090000765 processed proteins & peptides Proteins 0.000 description 9
239000012453 solvate Substances 0.000 description 9
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
239000002585 base Substances 0.000 description 8
238000010790 dilution Methods 0.000 description 8
239000012895 dilution Substances 0.000 description 8
238000000338 in vitro Methods 0.000 description 8
230000005764 inhibitory process Effects 0.000 description 8
238000002560 therapeutic procedure Methods 0.000 description 8
239000000463 material Substances 0.000 description 7
238000012360 testing method Methods 0.000 description 7
GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 6
239000005695 Ammonium acetate Substances 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
102000018233 Fibroblast Growth Factor Human genes 0.000 description 6
108050007372 Fibroblast Growth Factor Proteins 0.000 description 6
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
235000019257 ammonium acetate Nutrition 0.000 description 6
229940043376 ammonium acetate Drugs 0.000 description 6
239000000872 buffer Substances 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
239000012043 crude product Substances 0.000 description 6
CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 6
ROORDVPLFPIABK-UHFFFAOYSA-N diphenyl carbonate Chemical compound C=1C=CC=CC=1OC(=O)OC1=CC=CC=C1 ROORDVPLFPIABK-UHFFFAOYSA-N 0.000 description 6
208000035475 disorder Diseases 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
229940126864 fibroblast growth factor Drugs 0.000 description 6
150000002513 isocyanates Chemical class 0.000 description 6
239000002480 mineral oil Substances 0.000 description 6
235000010446 mineral oil Nutrition 0.000 description 6
239000007858 starting material Substances 0.000 description 6
125000001424 substituent group Chemical group 0.000 description 6
QAPSNMNOIOSXSQ-YNEHKIRRSA-N 1-[(2r,4s,5r)-4-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O[Si](C)(C)C(C)(C)C)C1 QAPSNMNOIOSXSQ-YNEHKIRRSA-N 0.000 description 5
102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 5
101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
125000004429 atom Chemical group 0.000 description 5
WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Substances O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
238000009472 formulation Methods 0.000 description 5
230000002401 inhibitory effect Effects 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000007937 lozenge Substances 0.000 description 5
229910052751 metal Inorganic materials 0.000 description 5
239000002184 metal Substances 0.000 description 5
230000003287 optical effect Effects 0.000 description 5
239000003960 organic solvent Substances 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
239000003755 preservative agent Substances 0.000 description 5
102000005962 receptors Human genes 0.000 description 5
108020003175 receptors Proteins 0.000 description 5
239000012321 sodium triacetoxyborohydride Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
239000003826 tablet Substances 0.000 description 5
210000001519 tissue Anatomy 0.000 description 5
238000004704 ultra performance liquid chromatography Methods 0.000 description 5
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 4
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 4
OGAMEMYFVKKANA-UHFFFAOYSA-N 6-amino-4-chloropyridine-3-carbonitrile Chemical compound NC1=CC(Cl)=C(C#N)C=N1 OGAMEMYFVKKANA-UHFFFAOYSA-N 0.000 description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
108091008794 FGF receptors Proteins 0.000 description 4
102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 4
101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 4
239000007995 HEPES buffer Substances 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 4
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
239000002246 antineoplastic agent Substances 0.000 description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
238000004090 dissolution Methods 0.000 description 4
239000000796 flavoring agent Substances 0.000 description 4
235000013355 food flavoring agent Nutrition 0.000 description 4
239000007789 gas Substances 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
238000011534 incubation Methods 0.000 description 4
230000000155 isotopic effect Effects 0.000 description 4
239000000314 lubricant Substances 0.000 description 4
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 4
UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000007921 spray Substances 0.000 description 4
239000003381 stabilizer Substances 0.000 description 4
208000024891 symptom Diseases 0.000 description 4
229910052725 zinc Inorganic materials 0.000 description 4
239000011701 zinc Substances 0.000 description 4
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 3
PIZHFBODNLEQBL-UHFFFAOYSA-N 2,2-diethoxy-1-phenylethanone Chemical compound CCOC(OCC)C(=O)C1=CC=CC=C1 PIZHFBODNLEQBL-UHFFFAOYSA-N 0.000 description 3
YMHHPDVFOJDHMH-LURJTMIESA-N 4-[(3S)-oxolan-3-yl]oxypyrimidin-2-amine Chemical compound Nc1nccc(O[C@H]2CCOC2)n1 YMHHPDVFOJDHMH-LURJTMIESA-N 0.000 description 3
CXBLQEIODBBSQD-UHFFFAOYSA-N 4-methylpiperidin-4-ol Chemical compound CC1(O)CCNCC1 CXBLQEIODBBSQD-UHFFFAOYSA-N 0.000 description 3
PJAYZQCDQDWOHK-UHFFFAOYSA-N 6-amino-4-(2-methoxyethoxy)pyridine-3-carbonitrile Chemical compound COCCOc1cc(N)ncc1C#N PJAYZQCDQDWOHK-UHFFFAOYSA-N 0.000 description 3
241000349731 Afzelia bipindensis Species 0.000 description 3
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 3
102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 3
101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 3
101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 3
102000003815 Interleukin-11 Human genes 0.000 description 3
108090000177 Interleukin-11 Proteins 0.000 description 3
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 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
101150003085 Pdcl gene Proteins 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
102000001253 Protein Kinase Human genes 0.000 description 3
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 3
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 3
102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
235000021355 Stearic acid Nutrition 0.000 description 3
150000001241 acetals Chemical group 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
230000004913 activation Effects 0.000 description 3
239000000043 antiallergic agent Substances 0.000 description 3
239000000611 antibody drug conjugate Substances 0.000 description 3
229940049595 antibody-drug conjugate Drugs 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
238000005119 centrifugation Methods 0.000 description 3
238000000576 coating method Methods 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
238000001914 filtration Methods 0.000 description 3
238000003682 fluorination reaction Methods 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
239000006260 foam Substances 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
229910052737 gold Inorganic materials 0.000 description 3
239000010931 gold Substances 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
150000004677 hydrates Chemical class 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000011065 in-situ storage Methods 0.000 description 3
229940074383 interleukin-11 Drugs 0.000 description 3
239000008101 lactose Substances 0.000 description 3
230000000670 limiting effect Effects 0.000 description 3
IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 3
230000005012 migration Effects 0.000 description 3
238000013508 migration Methods 0.000 description 3
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
229940127084 other anti-cancer agent Drugs 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
108060006633 protein kinase Proteins 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
239000011347 resin Substances 0.000 description 3
229920005989 resin Polymers 0.000 description 3
238000004007 reversed phase HPLC Methods 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
239000008107 starch Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
239000008117 stearic acid Substances 0.000 description 3
238000006467 substitution reaction Methods 0.000 description 3
WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 3
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 3
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 2
XDPCNPCKDGQBAN-BYPYZUCNSA-N (3s)-oxolan-3-ol Chemical compound O[C@H]1CCOC1 XDPCNPCKDGQBAN-BYPYZUCNSA-N 0.000 description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
GIKMWFAAEIACRF-UHFFFAOYSA-N 2,4,5-trichloropyrimidine Chemical compound ClC1=NC=C(Cl)C(Cl)=N1 GIKMWFAAEIACRF-UHFFFAOYSA-N 0.000 description 2
GBBSAMQTQCPOBF-UHFFFAOYSA-N 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane Chemical compound CB1OB(C)OB(C)O1 GBBSAMQTQCPOBF-UHFFFAOYSA-N 0.000 description 2
ZSUYSRCKBIRRNE-UHFFFAOYSA-N 2,5-dichloro-4-(oxolan-3-yloxy)pyrimidine Chemical compound ClC1=NC=C(Cl)C(OC2COCC2)=N1 ZSUYSRCKBIRRNE-UHFFFAOYSA-N 0.000 description 2
MQNLDEFVGJJXAY-YFKPBYRVSA-N 2,5-dichloro-4-[(2S)-1-methoxypropan-2-yl]oxypyrimidine Chemical compound COC[C@H](C)Oc1nc(Cl)ncc1Cl MQNLDEFVGJJXAY-YFKPBYRVSA-N 0.000 description 2
IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 2
SEUSFEKWVIFWTN-UHFFFAOYSA-N 2-aminopyrimidine-5-carbonitrile Chemical compound NC1=NC=C(C#N)C=N1 SEUSFEKWVIFWTN-UHFFFAOYSA-N 0.000 description 2
QVKFHPVLGNXPIT-UHFFFAOYSA-N 2-chloro-N-(2-methoxyethyl)-5-(trifluoromethyl)pyridin-4-amine Chemical compound COCCNc1cc(Cl)ncc1C(F)(F)F QVKFHPVLGNXPIT-UHFFFAOYSA-N 0.000 description 2
ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
JKWOMFWJCIOWDB-UHFFFAOYSA-N 4-N-(2-methoxyethyl)-2-N-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyridine-2,4-diamine Chemical compound COCCNc1cc(NCc2ccc(OC)cc2)ncc1C(F)(F)F JKWOMFWJCIOWDB-UHFFFAOYSA-N 0.000 description 2
LISISXJYGIZUEL-UHFFFAOYSA-N 4-fluoro-5-iodopyridin-2-amine Chemical compound NC1=CC(F)=C(I)C=N1 LISISXJYGIZUEL-UHFFFAOYSA-N 0.000 description 2
WCCFLOQQACDOAX-UHFFFAOYSA-N 4-fluoropyridin-2-amine Chemical compound NC1=CC(F)=CC=N1 WCCFLOQQACDOAX-UHFFFAOYSA-N 0.000 description 2
GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 description 2
BRGLPQOKZAJJEP-YFKPBYRVSA-N 5-bromo-4-[(3S)-oxolan-3-yl]oxypyrimidin-2-amine Chemical compound Nc1ncc(Br)c(O[C@H]2CCOC2)n1 BRGLPQOKZAJJEP-YFKPBYRVSA-N 0.000 description 2
AJJJJFDZNUCYTB-UHFFFAOYSA-N 5-chloro-4-(oxolan-3-yloxy)pyrimidin-2-amine Chemical compound NC1=NC=C(Cl)C(OC2COCC2)=N1 AJJJJFDZNUCYTB-UHFFFAOYSA-N 0.000 description 2
QUMVMVOEYFDDJD-UHFFFAOYSA-N 6-amino-4-(1-azabicyclo[2.2.2]octan-3-yloxy)pyridine-3-carbonitrile Chemical compound Nc1cc(OC2CN3CCC2CC3)c(cn1)C#N QUMVMVOEYFDDJD-UHFFFAOYSA-N 0.000 description 2
PDXLDEANFZSJBD-UHFFFAOYSA-N 6-amino-4-[2-(dimethylamino)ethoxy]pyridine-3-carbonitrile Chemical compound CN(C)CCOc1cc(N)ncc1C#N PDXLDEANFZSJBD-UHFFFAOYSA-N 0.000 description 2
KDVBYUUGYXUXNL-UHFFFAOYSA-N 6-aminopyridine-3-carbonitrile Chemical compound NC1=CC=C(C#N)C=N1 KDVBYUUGYXUXNL-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-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
CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
102000003903 Cyclin-dependent kinases Human genes 0.000 description 2
108090000266 Cyclin-dependent kinases Proteins 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
102000001301 EGF receptor Human genes 0.000 description 2
108060006698 EGF receptor Proteins 0.000 description 2
238000002965 ELISA Methods 0.000 description 2
102000003951 Erythropoietin Human genes 0.000 description 2
108090000394 Erythropoietin Proteins 0.000 description 2
102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
102000002812 Heat-Shock Proteins Human genes 0.000 description 2
108010004889 Heat-Shock Proteins Proteins 0.000 description 2
102000003964 Histone deacetylase Human genes 0.000 description 2
108090000353 Histone deacetylase Proteins 0.000 description 2
101000932478 Homo sapiens Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 2
101000610605 Homo sapiens Tumor necrosis factor receptor superfamily member 10A Proteins 0.000 description 2
101000610604 Homo sapiens Tumor necrosis factor receptor superfamily member 10B Proteins 0.000 description 2
206010020751 Hypersensitivity Diseases 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 2
206010028813 Nausea Diseases 0.000 description 2
108700020796 Oncogene Proteins 0.000 description 2
108091007960 PI3Ks Proteins 0.000 description 2
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 2
108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 2
102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
229920001213 Polysorbate 20 Polymers 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
241000288906 Primates Species 0.000 description 2
RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
229940079156 Proteasome inhibitor Drugs 0.000 description 2
108091008611 Protein Kinase B Proteins 0.000 description 2
102000003923 Protein Kinase C Human genes 0.000 description 2
108090000315 Protein Kinase C Proteins 0.000 description 2
102000005765 Proto-Oncogene Proteins c-akt Human genes 0.000 description 2
102000053067 Pyruvate Dehydrogenase Acetyl-Transferring Kinase Human genes 0.000 description 2
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 2
241000700159 Rattus Species 0.000 description 2
102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
102000036693 Thrombopoietin Human genes 0.000 description 2
108010041111 Thrombopoietin Proteins 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
102100040113 Tumor necrosis factor receptor superfamily member 10A Human genes 0.000 description 2
102100040112 Tumor necrosis factor receptor superfamily member 10B Human genes 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
101710159466 [Pyruvate dehydrogenase (acetyl-transferring)] kinase, mitochondrial Proteins 0.000 description 2
RSWGJHLUYNHPMX-ONCXSQPRSA-N abietic acid Chemical compound C([C@@H]12)CC(C(C)C)=CC1=CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(O)=O RSWGJHLUYNHPMX-ONCXSQPRSA-N 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
239000012190 activator Substances 0.000 description 2
239000002671 adjuvant Substances 0.000 description 2
239000003463 adsorbent Substances 0.000 description 2
239000000783 alginic acid Substances 0.000 description 2
235000010443 alginic acid Nutrition 0.000 description 2
229920000615 alginic acid Polymers 0.000 description 2
229960001126 alginic acid Drugs 0.000 description 2
150000004781 alginic acids Chemical class 0.000 description 2
239000003513 alkali Substances 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
239000003242 anti bacterial agent Substances 0.000 description 2
239000002111 antiemetic agent Substances 0.000 description 2
229940125683 antiemetic agent Drugs 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
230000008901 benefit Effects 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
239000002981 blocking agent Substances 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910000019 calcium carbonate Inorganic materials 0.000 description 2
239000001506 calcium phosphate Substances 0.000 description 2
229910000389 calcium phosphate Inorganic materials 0.000 description 2
235000011010 calcium phosphates Nutrition 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 2
235000015165 citric acid Nutrition 0.000 description 2
239000003086 colorant Substances 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
238000002648 combination therapy Methods 0.000 description 2
WJYJULOBJLLPER-UHFFFAOYSA-N copper(1+);trifluoromethane Chemical compound [Cu+].F[C-](F)F WJYJULOBJLLPER-UHFFFAOYSA-N 0.000 description 2
230000008878 coupling Effects 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
DRIWHLGVWDOZBP-UHFFFAOYSA-N cyclohexa-1,3-dien-1-yl formate Chemical compound O=COC1=CC=CCC1 DRIWHLGVWDOZBP-UHFFFAOYSA-N 0.000 description 2
230000001120 cytoprotective effect Effects 0.000 description 2
231100000599 cytotoxic agent Toxicity 0.000 description 2
230000005595 deprotonation Effects 0.000 description 2
238000010537 deprotonation reaction Methods 0.000 description 2
150000001975 deuterium Chemical group 0.000 description 2
238000011161 development Methods 0.000 description 2
230000018109 developmental process Effects 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
229940000406 drug candidate Drugs 0.000 description 2
238000005401 electroluminescence Methods 0.000 description 2
239000003995 emulsifying agent Substances 0.000 description 2
238000005516 engineering process Methods 0.000 description 2
239000003623 enhancer Substances 0.000 description 2
229940105423 erythropoietin Drugs 0.000 description 2
230000002349 favourable effect Effects 0.000 description 2
239000000835 fiber Substances 0.000 description 2
102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 2
239000011888 foil Substances 0.000 description 2
235000003599 food sweetener Nutrition 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
239000011521 glass Substances 0.000 description 2
239000008187 granular material Substances 0.000 description 2
239000001963 growth medium Substances 0.000 description 2
238000005658 halogenation reaction Methods 0.000 description 2
150000002430 hydrocarbons Chemical group 0.000 description 2
239000002955 immunomodulating agent Substances 0.000 description 2
229940121354 immunomodulator Drugs 0.000 description 2
239000003701 inert diluent Substances 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
229940043355 kinase inhibitor Drugs 0.000 description 2
239000003446 ligand Substances 0.000 description 2
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
239000007791 liquid phase Substances 0.000 description 2
239000012139 lysis buffer Substances 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
229960002510 mandelic acid Drugs 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
230000002503 metabolic effect Effects 0.000 description 2
GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
239000003226 mitogen Substances 0.000 description 2
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
230000008693 nausea Effects 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 2
230000026731 phosphorylation Effects 0.000 description 2
238000006366 phosphorylation reaction Methods 0.000 description 2
239000003757 phosphotransferase inhibitor Substances 0.000 description 2
125000003386 piperidinyl group Chemical group 0.000 description 2
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
238000002600 positron emission tomography Methods 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 2
239000002243 precursor Substances 0.000 description 2
150000003138 primary alcohols Chemical class 0.000 description 2
102000004196 processed proteins & peptides Human genes 0.000 description 2
238000012545 processing Methods 0.000 description 2
230000000069 prophylactic effect Effects 0.000 description 2
239000003207 proteasome inhibitor Substances 0.000 description 2
239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 2
235000018102 proteins Nutrition 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 2
229940044601 receptor agonist Drugs 0.000 description 2
239000000018 receptor agonist Substances 0.000 description 2
108091006082 receptor inhibitors Proteins 0.000 description 2
230000009467 reduction Effects 0.000 description 2
238000006722 reduction reaction Methods 0.000 description 2
238000006268 reductive amination reaction Methods 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
238000013207 serial dilution Methods 0.000 description 2
238000002603 single-photon emission computed tomography Methods 0.000 description 2
DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
230000003595 spectral effect Effects 0.000 description 2
230000006641 stabilisation Effects 0.000 description 2
238000011105 stabilization Methods 0.000 description 2
239000011550 stock solution Substances 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000003765 sweetening agent Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
235000012222 talc Nutrition 0.000 description 2
230000017423 tissue regeneration Effects 0.000 description 2
230000000699 topical effect Effects 0.000 description 2
238000012546 transfer Methods 0.000 description 2
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 2
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
241001430294 unidentified retrovirus Species 0.000 description 2
239000000080 wetting agent Substances 0.000 description 2
KJZLJGZZDNGGCA-UHFFFAOYSA-N (1-methylpiperidin-4-yl)methanol Chemical compound CN1CCC(CO)CC1 KJZLJGZZDNGGCA-UHFFFAOYSA-N 0.000 description 1
XDPCNPCKDGQBAN-SCSAIBSYSA-N (3r)-oxolan-3-ol Chemical compound O[C@@H]1CCOC1 XDPCNPCKDGQBAN-SCSAIBSYSA-N 0.000 description 1
125000004191 (C1-C6) alkoxy group Chemical group 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
ULVSHNOGEVXRDR-UHFFFAOYSA-N 1,1-dimethoxypropan-2-one Chemical compound COC(OC)C(C)=O ULVSHNOGEVXRDR-UHFFFAOYSA-N 0.000 description 1
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
FLVFPAIGVBQGET-UHFFFAOYSA-N 1-methylpyrrolidin-3-ol Chemical compound CN1CCC(O)C1 FLVFPAIGVBQGET-UHFFFAOYSA-N 0.000 description 1
INAPMGSXUVUWAF-PTQMNWPWSA-N 1D-myo-inositol 3-phosphate Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](OP(O)(O)=O)[C@@H](O)[C@@H]1O INAPMGSXUVUWAF-PTQMNWPWSA-N 0.000 description 1
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
SUDDXMSROFLAQH-UHFFFAOYSA-N 2,3-dihydroxy-2-methylbutanedioic acid Chemical compound OC(=O)C(O)(C)C(O)C(O)=O SUDDXMSROFLAQH-UHFFFAOYSA-N 0.000 description 1
HQEZKTVEZYMLRK-UHFFFAOYSA-N 2,4-dichloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CN=C(Cl)C=C1Cl HQEZKTVEZYMLRK-UHFFFAOYSA-N 0.000 description 1
WWVLDJAVSQZSKO-UHFFFAOYSA-N 2,5-dichloro-n-(2-propan-2-ylsulfonylphenyl)pyrimidin-4-amine Chemical compound CC(C)S(=O)(=O)C1=CC=CC=C1NC1=NC(Cl)=NC=C1Cl WWVLDJAVSQZSKO-UHFFFAOYSA-N 0.000 description 1
MXZROAOUCUVNHX-UHFFFAOYSA-N 2-Aminopropanol Chemical compound CCC(N)O MXZROAOUCUVNHX-UHFFFAOYSA-N 0.000 description 1
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
DYBBGZCJHXJEFY-ZETCQYMHSA-N 2-amino-4-[(3S)-oxolan-3-yl]oxypyrimidine-5-carbonitrile Chemical compound Nc1ncc(C#N)c(O[C@H]2CCOC2)n1 DYBBGZCJHXJEFY-ZETCQYMHSA-N 0.000 description 1
NXMFJCRMSDRXLD-UHFFFAOYSA-N 2-aminopyridine-3-carbaldehyde Chemical compound NC1=NC=CC=C1C=O NXMFJCRMSDRXLD-UHFFFAOYSA-N 0.000 description 1
CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 1
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
SAOSCTYRONNFTC-UHFFFAOYSA-N 2-methyl-decanoic acid Chemical compound CCCCCCCCC(C)C(O)=O SAOSCTYRONNFTC-UHFFFAOYSA-N 0.000 description 1
WVKPYYLOFMTDHB-UHFFFAOYSA-N 2-norbornyl radical Chemical group C1CC2[CH]CC1C2 WVKPYYLOFMTDHB-UHFFFAOYSA-N 0.000 description 1
VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
XDPCNPCKDGQBAN-UHFFFAOYSA-N 3-hydroxytetrahydrofuran Chemical compound OC1CCOC1 XDPCNPCKDGQBAN-UHFFFAOYSA-N 0.000 description 1
102100037263 3-phosphoinositide-dependent protein kinase 1 Human genes 0.000 description 1
IVLICPVPXWEGCA-UHFFFAOYSA-N 3-quinuclidinol Chemical compound C1C[C@@H]2C(O)C[N@]1CC2 IVLICPVPXWEGCA-UHFFFAOYSA-N 0.000 description 1
CRRAQLWJVYODCL-UHFFFAOYSA-N 4,5-dichloropyridin-2-amine Chemical compound NC1=CC(Cl)=C(Cl)C=N1 CRRAQLWJVYODCL-UHFFFAOYSA-N 0.000 description 1
PRUCLTZNSFKRCO-UHFFFAOYSA-N 4-(2-methoxyethylamino)pyridine-3-carbonitrile Chemical compound C(#N)C=1C(=CC=NC=1)NCCOC PRUCLTZNSFKRCO-UHFFFAOYSA-N 0.000 description 1
RLZOSOUNZRMPQL-UHFFFAOYSA-N 4-N-(2-methoxyethyl)-5-(trifluoromethyl)pyridine-2,4-diamine Chemical compound COCCNc1cc(N)ncc1C(F)(F)F RLZOSOUNZRMPQL-UHFFFAOYSA-N 0.000 description 1
ZMOSSSKZBGTPED-QMMMGPOBSA-N 4-[(3S)-oxolan-3-yl]oxypyridin-2-amine Chemical compound O1C[C@H](CC1)OC1=CC(=NC=C1)N ZMOSSSKZBGTPED-QMMMGPOBSA-N 0.000 description 1
SVGCHZLCVBUEID-UHFFFAOYSA-N 4-[(dimethylamino)methyl]piperidin-4-ol Chemical compound CN(C)CC1(O)CCNCC1 SVGCHZLCVBUEID-UHFFFAOYSA-N 0.000 description 1
GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
LDFNTYITPGQXDO-UHFFFAOYSA-N 4-chloro-N-(2-methoxyethyl)-5-(trifluoromethyl)pyridin-2-amine Chemical compound COCCNc1cc(Cl)c(cn1)C(F)(F)F LDFNTYITPGQXDO-UHFFFAOYSA-N 0.000 description 1
DBGFGNCFYUNXLD-UHFFFAOYSA-N 4-chloropyrimidin-2-amine Chemical compound NC1=NC=CC(Cl)=N1 DBGFGNCFYUNXLD-UHFFFAOYSA-N 0.000 description 1
229960000549 4-dimethylaminophenol Drugs 0.000 description 1
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
BIUGUCBZWRUHGY-UHFFFAOYSA-N 4-fluoropyridine-3-carbonitrile Chemical compound FC1=CC=NC=C1C#N BIUGUCBZWRUHGY-UHFFFAOYSA-N 0.000 description 1
RSGVKIIEIXOMPY-UHFFFAOYSA-N 5-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=CC=C(C(F)(F)F)C=N1 RSGVKIIEIXOMPY-UHFFFAOYSA-N 0.000 description 1
DDOFUMWLNSICHU-UHFFFAOYSA-N 5-bromo-4-chloropyridin-2-amine Chemical compound NC1=CC(Cl)=C(Br)C=N1 DDOFUMWLNSICHU-UHFFFAOYSA-N 0.000 description 1
CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 1
RFTHOIRJUUIVOK-YFKPBYRVSA-N 5-chloro-4-[(2S)-1-methoxypropan-2-yl]oxypyrimidin-2-amine Chemical compound COC[C@H](C)Oc1nc(N)ncc1Cl RFTHOIRJUUIVOK-YFKPBYRVSA-N 0.000 description 1
VRHVIADZKHHHQX-LURJTMIESA-N 5-chloro-4-[(3S)-oxolan-3-yl]oxypyridin-2-amine Chemical compound Nc1cc(O[C@H]2CCOC2)c(Cl)cn1 VRHVIADZKHHHQX-LURJTMIESA-N 0.000 description 1
AJJJJFDZNUCYTB-YFKPBYRVSA-N 5-chloro-4-[(3S)-oxolan-3-yl]oxypyrimidin-2-amine Chemical compound Nc1ncc(Cl)c(O[C@H]2CCOC2)n1 AJJJJFDZNUCYTB-YFKPBYRVSA-N 0.000 description 1
KSYGTHLJZRSQMY-UHFFFAOYSA-N 6-amino-4-(1-methoxypropan-2-yloxy)pyridine-3-carbonitrile Chemical compound COCC(C)Oc1cc(N)ncc1C#N KSYGTHLJZRSQMY-UHFFFAOYSA-N 0.000 description 1
WEXAADVAVBAXPC-UHFFFAOYSA-N 6-amino-4-(1-methylpyrrolidin-3-yl)oxypyridine-3-carbonitrile Chemical compound CN1CCC(C1)Oc1cc(N)ncc1C#N WEXAADVAVBAXPC-UHFFFAOYSA-N 0.000 description 1
ZOUKWONJNJOORG-UHFFFAOYSA-N 6-amino-4-(2,2,2-trifluoroethoxy)pyridine-3-carbonitrile Chemical compound Nc1cc(OCC(F)(F)F)c(cn1)C#N ZOUKWONJNJOORG-UHFFFAOYSA-N 0.000 description 1
QGKUZOVUGOISIH-UHFFFAOYSA-N 6-amino-4-(2-methoxyethylamino)pyridine-3-carbonitrile Chemical compound COCCNc1cc(N)ncc1C#N QGKUZOVUGOISIH-UHFFFAOYSA-N 0.000 description 1
XHVXZQFCHMUZGX-UHFFFAOYSA-N 6-amino-4-(4-hydroxy-4-methylpiperidin-1-yl)pyridine-3-carbonitrile Chemical compound CC1(O)CCN(CC1)c1cc(N)ncc1C#N XHVXZQFCHMUZGX-UHFFFAOYSA-N 0.000 description 1
BCTSPEMJAISKJN-UHFFFAOYSA-N 6-amino-4-(oxetan-2-ylmethoxy)pyridine-3-carbonitrile Chemical compound Nc1cc(OCC2CCO2)c(cn1)C#N BCTSPEMJAISKJN-UHFFFAOYSA-N 0.000 description 1
ICISITHBUZLFRN-UHFFFAOYSA-N 6-amino-4-(oxolan-2-ylmethoxy)pyridine-3-carbonitrile Chemical compound Nc1cc(OCC2CCCO2)c(cn1)C#N ICISITHBUZLFRN-UHFFFAOYSA-N 0.000 description 1
YYBUSUYEYXBRDI-UHFFFAOYSA-N 6-amino-4-[(1-methylpiperidin-4-yl)methoxy]pyridine-3-carbonitrile Chemical compound CN1CCC(COc2cc(N)ncc2C#N)CC1 YYBUSUYEYXBRDI-UHFFFAOYSA-N 0.000 description 1
ISINKLHDYOSKPW-MRVPVSSYSA-N 6-amino-4-[(3R)-oxolan-3-yl]oxypyridine-3-carbonitrile Chemical compound Nc1cc(O[C@@H]2CCOC2)c(cn1)C#N ISINKLHDYOSKPW-MRVPVSSYSA-N 0.000 description 1
PCJYJVMUQITUGR-UHFFFAOYSA-N 6-amino-4-[4-[(dimethylamino)methyl]-4-hydroxypiperidin-1-yl]pyridine-3-carbonitrile Chemical compound CN(C)CC1(O)CCN(CC1)c1cc(N)ncc1C#N PCJYJVMUQITUGR-UHFFFAOYSA-N 0.000 description 1
YLHHTEDISYPMIS-UHFFFAOYSA-N 6-amino-4-ethoxypyridine-3-carbonitrile Chemical compound CCOc1cc(N)ncc1C#N YLHHTEDISYPMIS-UHFFFAOYSA-N 0.000 description 1
OTGDCHNSXQUISE-UHFFFAOYSA-N 6-bromo-3,4-dihydro-2h-pyrido[3,2-b][1,4]oxazine Chemical compound O1CCNC2=NC(Br)=CC=C21 OTGDCHNSXQUISE-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
HXVWJOVVANKRLI-UHFFFAOYSA-N 8-diazospiro[4.5]decane Chemical compound [N+](=[N-])=C1CCC2(CCCC2)CC1 HXVWJOVVANKRLI-UHFFFAOYSA-N 0.000 description 1
CYSPWCARDHRYJX-UHFFFAOYSA-N 9h-fluoren-1-amine Chemical group C12=CC=CC=C2CC2=C1C=CC=C2N CYSPWCARDHRYJX-UHFFFAOYSA-N 0.000 description 1
241000251468 Actinopterygii Species 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
241000272878 Apodiformes Species 0.000 description 1
229940123877 Aurora kinase inhibitor Drugs 0.000 description 1
102100038080 B-cell receptor CD22 Human genes 0.000 description 1
241001589086 Bellapiscis medius Species 0.000 description 1
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
229940122361 Bisphosphonate Drugs 0.000 description 1
206010005003 Bladder cancer Diseases 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
229940124204 C-kit inhibitor Drugs 0.000 description 1
102100024217 CAMPATH-1 antigen Human genes 0.000 description 1
229940124293 CD30 monoclonal antibody Drugs 0.000 description 1
101150013553 CD40 gene Proteins 0.000 description 1
108010065524 CD52 Antigen Proteins 0.000 description 1
241000283707 Capra Species 0.000 description 1
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
102000000844 Cell Surface Receptors Human genes 0.000 description 1
108010001857 Cell Surface Receptors Proteins 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
108010071942 Colony-Stimulating Factors Proteins 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
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
101710112752 Cytotoxin Proteins 0.000 description 1
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 1
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 1
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 1
229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 1
101000582926 Dictyostelium discoideum Probable serine/threonine-protein kinase PLK Proteins 0.000 description 1
206010061818 Disease progression Diseases 0.000 description 1
101150029707 ERBB2 gene Proteins 0.000 description 1
241000283073 Equus caballus Species 0.000 description 1
241001481760 Erethizon dorsatum Species 0.000 description 1
229940125408 FGFR4 inhibitor Drugs 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
102100031734 Fibroblast growth factor 19 Human genes 0.000 description 1
101710182387 Fibroblast growth factor receptor 4 Proteins 0.000 description 1
229940123414 Folate antagonist Drugs 0.000 description 1
229940123457 Free radical scavenger Drugs 0.000 description 1
108091006027 G proteins Proteins 0.000 description 1
102000030782 GTP binding Human genes 0.000 description 1
108091000058 GTP-Binding Proteins 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 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
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
NMJREATYWWNIKX-UHFFFAOYSA-N GnRH Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CC(C)C)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 NMJREATYWWNIKX-UHFFFAOYSA-N 0.000 description 1
239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
102000009465 Growth Factor Receptors Human genes 0.000 description 1
108010009202 Growth Factor Receptors Proteins 0.000 description 1
241000238631 Hexapoda Species 0.000 description 1
101000600756 Homo sapiens 3-phosphoinositide-dependent protein kinase 1 Proteins 0.000 description 1
101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 1
101100334744 Homo sapiens FGFR4 gene Proteins 0.000 description 1
101000846394 Homo sapiens Fibroblast growth factor 19 Proteins 0.000 description 1
101001059535 Homo sapiens Megakaryocyte-associated tyrosine-protein kinase Proteins 0.000 description 1
101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 1
101000896517 Homo sapiens Steroid 17-alpha-hydroxylase/17,20 lyase Proteins 0.000 description 1
102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
102000016844 Immunoglobulin-like domains Human genes 0.000 description 1
108050006430 Immunoglobulin-like domains Proteins 0.000 description 1
102000014150 Interferons Human genes 0.000 description 1
108010050904 Interferons Proteins 0.000 description 1
102000015696 Interleukins Human genes 0.000 description 1
108010063738 Interleukins Proteins 0.000 description 1
229940122245 Janus kinase inhibitor Drugs 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
229940082819 Luteinizing hormone releasing hormone (LHRH) agonist Drugs 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
102100037611 Lysophospholipase Human genes 0.000 description 1
102000043136 MAP kinase family Human genes 0.000 description 1
108091054455 MAP kinase family Proteins 0.000 description 1
229940083338 MDM2 inhibitor Drugs 0.000 description 1
239000012819 MDM2-Inhibitor Substances 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
102100028905 Megakaryocyte-associated tyrosine-protein kinase Human genes 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
101000856426 Mus musculus Cullin-7 Proteins 0.000 description 1
101100261153 Mus musculus Mpl gene Proteins 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
108010057466 NF-kappa B Proteins 0.000 description 1
102000003945 NF-kappa B Human genes 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
206010061902 Pancreatic neoplasm Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
241001494479 Pecora Species 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
229940122907 Phosphatase inhibitor Drugs 0.000 description 1
108010058864 Phospholipases A2 Proteins 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
206010035226 Plasma cell myeloma Diseases 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
239000004743 Polypropylene Substances 0.000 description 1
239000004365 Protease Substances 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
108010076504 Protein Sorting Signals Proteins 0.000 description 1
102000018471 Proto-Oncogene Proteins B-raf Human genes 0.000 description 1
108010091528 Proto-Oncogene Proteins B-raf Proteins 0.000 description 1
108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 1
102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 1
102100028286 Proto-oncogene tyrosine-protein kinase receptor Ret Human genes 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 1
239000012980 RPMI-1640 medium Substances 0.000 description 1
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
241000207929 Scutellaria Species 0.000 description 1
102100036077 Serine/threonine-protein kinase pim-1 Human genes 0.000 description 1
BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
208000000453 Skin Neoplasms Diseases 0.000 description 1
108050001286 Somatostatin Receptor Proteins 0.000 description 1
102000011096 Somatostatin receptor Human genes 0.000 description 1
108010015330 Steroid 17-alpha-Hydroxylase Proteins 0.000 description 1
102000001854 Steroid 17-alpha-Hydroxylase Human genes 0.000 description 1
102100021719 Steroid 17-alpha-hydroxylase/17,20 lyase Human genes 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
229930006000 Sucrose Natural products 0.000 description 1
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 1
229940123237 Taxane Drugs 0.000 description 1
239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
239000000317 Topoisomerase II Inhibitor Substances 0.000 description 1
RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
239000013504 Triton X-100 Substances 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
206010047700 Vomiting Diseases 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
239000003070 absorption delaying agent Substances 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
239000000370 acceptor Substances 0.000 description 1
125000004036 acetal group Chemical group 0.000 description 1
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 1
CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
238000009098 adjuvant therapy Methods 0.000 description 1
239000003470 adrenal cortex hormone Substances 0.000 description 1
238000001042 affinity chromatography Methods 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
239000000556 agonist Substances 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 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
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
238000005576 amination reaction Methods 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
239000003263 anabolic agent Substances 0.000 description 1
229940070021 anabolic steroids Drugs 0.000 description 1
230000033115 angiogenesis Effects 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
229940045799 anthracyclines and related substance Drugs 0.000 description 1
230000002280 anti-androgenic effect Effects 0.000 description 1
230000003474 anti-emetic effect Effects 0.000 description 1
229940046836 anti-estrogen Drugs 0.000 description 1
230000001833 anti-estrogenic effect Effects 0.000 description 1
230000003432 anti-folate effect Effects 0.000 description 1
230000000340 anti-metabolite Effects 0.000 description 1
230000001946 anti-microtubular Effects 0.000 description 1
230000001062 anti-nausea Effects 0.000 description 1
230000000118 anti-neoplastic effect Effects 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
239000000051 antiandrogen Substances 0.000 description 1
229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
229940127074 antifolate Drugs 0.000 description 1
239000003429 antifungal agent Substances 0.000 description 1
229940121375 antifungal agent Drugs 0.000 description 1
239000000739 antihistaminic agent Substances 0.000 description 1
229940125715 antihistaminic agent Drugs 0.000 description 1
229940100197 antimetabolite Drugs 0.000 description 1
239000002256 antimetabolite Substances 0.000 description 1
229940034982 antineoplastic agent Drugs 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
239000011260 aqueous acid Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
239000003886 aromatase inhibitor Substances 0.000 description 1
229940046844 aromatase inhibitors Drugs 0.000 description 1
238000003556 assay Methods 0.000 description 1
239000003719 aurora kinase inhibitor Substances 0.000 description 1
XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 description 1
125000002393 azetidinyl group Chemical group 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
238000012742 biochemical analysis Methods 0.000 description 1
239000012620 biological material Substances 0.000 description 1
230000031018 biological processes and functions Effects 0.000 description 1
230000008512 biological response Effects 0.000 description 1
YHNUDLCUIKMNSN-UHFFFAOYSA-N bis(1,2,4-triazol-1-yl)methanone Chemical compound C1=NC=NN1C(=O)N1C=NC=N1 YHNUDLCUIKMNSN-UHFFFAOYSA-N 0.000 description 1
150000004663 bisphosphonates Chemical class 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
230000014461 bone development Effects 0.000 description 1
230000031709 bromination Effects 0.000 description 1
238000005893 bromination reaction Methods 0.000 description 1
229940124630 bronchodilator Drugs 0.000 description 1
239000000168 bronchodilator agent Substances 0.000 description 1
239000006172 buffering agent 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
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
MXOSTENCGSDMRE-UHFFFAOYSA-N butyl-chloro-dimethylsilane Chemical compound CCCC[Si](C)(C)Cl MXOSTENCGSDMRE-UHFFFAOYSA-N 0.000 description 1
235000010216 calcium carbonate Nutrition 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
238000004364 calculation method Methods 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
235000011089 carbon dioxide Nutrition 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
229940045200 cardioprotective agent Drugs 0.000 description 1
239000012659 cardioprotective agent Substances 0.000 description 1
239000000969 carrier Substances 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
230000024245 cell differentiation Effects 0.000 description 1
230000010261 cell growth Effects 0.000 description 1
239000013592 cell lysate Substances 0.000 description 1
230000012292 cell migration Effects 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
OEUUFNIKLCFNLN-LLVKDONJSA-N chembl432481 Chemical compound OC(=O)[C@@]1(C)CSC(C=2C(=CC(O)=CC=2)O)=N1 OEUUFNIKLCFNLN-LLVKDONJSA-N 0.000 description 1
230000035605 chemotaxis Effects 0.000 description 1
239000012320 chlorinating reagent Substances 0.000 description 1
238000005660 chlorination reaction Methods 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
238000003181 co-melting Methods 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
229940047120 colony stimulating factors Drugs 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
239000013066 combination product Substances 0.000 description 1
229940127555 combination product Drugs 0.000 description 1
238000002591 computed tomography Methods 0.000 description 1
235000009508 confectionery Nutrition 0.000 description 1
239000000562 conjugate Substances 0.000 description 1
230000006552 constitutive activation Effects 0.000 description 1
239000012050 conventional carrier Substances 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
239000010949 copper Substances 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
239000003246 corticosteroid Substances 0.000 description 1
229960001334 corticosteroids Drugs 0.000 description 1
239000002537 cosmetic Substances 0.000 description 1
239000006071 cream Substances 0.000 description 1
238000006880 cross-coupling reaction Methods 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
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 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
229940127089 cytotoxic agent Drugs 0.000 description 1
239000002254 cytotoxic agent Substances 0.000 description 1
239000002619 cytotoxin Substances 0.000 description 1
238000007405 data analysis Methods 0.000 description 1
239000012649 demethylating agent Substances 0.000 description 1
238000006392 deoxygenation reaction Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 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
230000005750 disease progression Effects 0.000 description 1
239000002612 dispersion medium Substances 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
238000009826 distribution Methods 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
230000002222 downregulating effect Effects 0.000 description 1
229940112141 dry powder inhaler Drugs 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000000975 dye Substances 0.000 description 1
230000005684 electric field Effects 0.000 description 1
150000003885 epothilone B derivatives Chemical class 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
239000000328 estrogen antagonist Substances 0.000 description 1
239000002834 estrogen receptor modulator Substances 0.000 description 1
102000015694 estrogen receptors Human genes 0.000 description 1
108010038795 estrogen receptors Proteins 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
QUSNBJAOOMFDIB-UHFFFAOYSA-O ethylaminium Chemical compound CC[NH3+] QUSNBJAOOMFDIB-UHFFFAOYSA-O 0.000 description 1
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
SFNALCNOMXIBKG-UHFFFAOYSA-N ethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCO SFNALCNOMXIBKG-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
239000012091 fetal bovine serum Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
238000005187 foaming Methods 0.000 description 1
239000004052 folic acid antagonist Substances 0.000 description 1
238000006170 formylation reaction Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
108020001507 fusion proteins Proteins 0.000 description 1
102000037865 fusion proteins Human genes 0.000 description 1
229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000000499 gel Substances 0.000 description 1
238000001415 gene therapy Methods 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
229940046257 glyceryl phosphate Drugs 0.000 description 1
XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
229940035638 gonadotropin-releasing hormone Drugs 0.000 description 1
239000003979 granulating agent Substances 0.000 description 1
238000000227 grinding Methods 0.000 description 1
230000012010 growth Effects 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
230000002140 halogenating effect Effects 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
239000007902 hard capsule Substances 0.000 description 1
230000011132 hemopoiesis Effects 0.000 description 1
206010073071 hepatocellular carcinoma Diseases 0.000 description 1
231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
IKGLACJFEHSFNN-UHFFFAOYSA-N hydron;triethylazanium;trifluoride Chemical compound F.F.F.CCN(CC)CC IKGLACJFEHSFNN-UHFFFAOYSA-N 0.000 description 1
238000003384 imaging method Methods 0.000 description 1
239000000411 inducer Substances 0.000 description 1
239000007972 injectable composition Substances 0.000 description 1
229940079322 interferon Drugs 0.000 description 1
229940047122 interleukins Drugs 0.000 description 1
UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
239000012336 iodinating agent Substances 0.000 description 1
230000002083 iodinating effect Effects 0.000 description 1
230000026045 iodination Effects 0.000 description 1
238000006192 iodination reaction Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 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
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
239000007951 isotonicity adjuster Substances 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
150000003951 lactams Chemical class 0.000 description 1
108020001756 ligand binding domains Proteins 0.000 description 1
230000006517 limb development Effects 0.000 description 1
238000012417 linear regression Methods 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
239000006210 lotion Substances 0.000 description 1
229960003646 lysine Drugs 0.000 description 1
229940124302 mTOR inhibitor Drugs 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
235000019359 magnesium stearate Nutrition 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
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000008774 maternal effect Effects 0.000 description 1
239000002609 medium Substances 0.000 description 1
229960003194 meglumine Drugs 0.000 description 1
239000012528 membrane Substances 0.000 description 1
238000006263 metalation reaction Methods 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
238000004452 microanalysis Methods 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000003607 modifier Substances 0.000 description 1
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
RPAWVEMNAJPPEL-UHFFFAOYSA-N morpholine;thiomorpholine Chemical group C1COCCN1.C1CSCCN1 RPAWVEMNAJPPEL-UHFFFAOYSA-N 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
201000000050 myeloid neoplasm Diseases 0.000 description 1
VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
KNCQHMMKDOIHRT-UHFFFAOYSA-N n,n-dimethyl-1-morpholin-2-ylmethanamine Chemical compound CN(C)CC1CNCCO1 KNCQHMMKDOIHRT-UHFFFAOYSA-N 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000006199 nebulizer Substances 0.000 description 1
239000004090 neuroprotective agent Substances 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000003865 nucleic acid synthesis inhibitor Substances 0.000 description 1
102000039446 nucleic acids Human genes 0.000 description 1
108020004707 nucleic acids Proteins 0.000 description 1
150000007523 nucleic acids Chemical class 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
239000002674 ointment Substances 0.000 description 1
238000006384 oligomerization reaction Methods 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
210000002997 osteoclast Anatomy 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
150000004893 oxazines Chemical class 0.000 description 1
125000003566 oxetanyl group Chemical group 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
238000010651 palladium-catalyzed cross coupling reaction Methods 0.000 description 1
201000002528 pancreatic cancer Diseases 0.000 description 1
208000008443 pancreatic carcinoma Diseases 0.000 description 1
229960002566 papillomavirus vaccine Drugs 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
235000019371 penicillin G benzathine Nutrition 0.000 description 1
125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
JQQSUOJIMKJQHS-UHFFFAOYSA-N pentaphenyl group Chemical group C1=CC=CC2=CC3=CC=C4C=C5C=CC=CC5=CC4=C3C=C12 JQQSUOJIMKJQHS-UHFFFAOYSA-N 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
229960005141 piperazine Drugs 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
238000004237 preparative chromatography Methods 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
238000007639 printing Methods 0.000 description 1
230000000861 pro-apoptotic effect Effects 0.000 description 1
239000000186 progesterone Substances 0.000 description 1
229960003387 progesterone Drugs 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
239000003380 propellant Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
230000004952 protein activity Effects 0.000 description 1
239000003197 protein kinase B inhibitor Substances 0.000 description 1
238000010926 purge Methods 0.000 description 1
QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
238000010791 quenching Methods 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
239000002516 radical scavenger Substances 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
238000001959 radiotherapy Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000007634 remodeling Methods 0.000 description 1
BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
238000009738 saturating Methods 0.000 description 1
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
238000000926 separation method Methods 0.000 description 1
229910052709 silver Inorganic materials 0.000 description 1
239000004332 silver Substances 0.000 description 1
201000000849 skin cancer Diseases 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229940054269 sodium pyruvate Drugs 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000007962 solid dispersion Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
241000894007 species Species 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000012089 stop solution Substances 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
238000000859 sublimation Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
230000000475 sunscreen effect Effects 0.000 description 1
239000000516 sunscreening agent Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
VULHROMOFQYLNP-UHFFFAOYSA-N tert-butyl 2-methyldecanoate Chemical compound CCCCCCCCC(C)C(=O)OC(C)(C)C VULHROMOFQYLNP-UHFFFAOYSA-N 0.000 description 1
WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
GKWGBMHXVRSFRT-UHFFFAOYSA-N tert-butyl n-[2-(methylamino)ethyl]carbamate Chemical compound CNCCNC(=O)OC(C)(C)C GKWGBMHXVRSFRT-UHFFFAOYSA-N 0.000 description 1
MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
238000010998 test method Methods 0.000 description 1
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
238000010257 thawing Methods 0.000 description 1
231100001274 therapeutic index Toxicity 0.000 description 1
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
230000007838 tissue remodeling Effects 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
231100000155 toxicity by organ Toxicity 0.000 description 1
230000007675 toxicity by organ Effects 0.000 description 1
230000037317 transdermal delivery Effects 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
238000006692 trifluoromethylation reaction Methods 0.000 description 1
230000001960 triggered effect Effects 0.000 description 1
PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
238000005533 tritiation Methods 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
230000005740 tumor formation Effects 0.000 description 1
229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
201000005112 urinary bladder cancer Diseases 0.000 description 1
229960005486 vaccine Drugs 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
230000008673 vomiting Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000001993 wax Substances 0.000 description 1
238000009736 wetting Methods 0.000 description 1
230000029663 wound healing Effects 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

TW103136873A 2013-10-25 2014-10-24 作為ｆｇｆｒ４抑制劑之稠環雙環吡啶基衍生物 TWI673268B (zh)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
??PCT/CN2013/086003		2013-10-25
CN2013086003		2013-10-25

Publications (2)

Publication Number	Publication Date
TW201605853A TW201605853A (zh)	2016-02-16
TWI673268B true TWI673268B (zh)	2019-10-01

Family

ID=53491699

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
TW103136873A TWI673268B (zh)	2013-10-25	2014-10-24	作為ｆｇｆｒ４抑制劑之稠環雙環吡啶基衍生物
TW108124006A TWI690528B (zh)	2013-10-25	2014-10-24	稠環雙環吡啶基衍生物

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
TW108124006A TWI690528B (zh)	2013-10-25	2014-10-24	稠環雙環吡啶基衍生物

Country Status (4)

Country	Link
AR (1)	AR098145A1 (fr)
MA (1)	MA39054B1 (fr)
TW (2)	TWI673268B (fr)
UY (1)	UY35792A (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2010119284A1 (fr) *	2009-04-15	2010-10-21	Astex Therapeutics Limited	Dérivés hétérocyclyle bicycliques en tant qu'inhibiteurs des fgfr kinases destinés à un usage thérapeutique
WO2013061080A1 (fr) *	2011-10-28	2013-05-02	Astex Therapeutics Limited	Pyridopyrazines anti-cancéreuses par l'inhibition de kinases de fgfr

2014
- 2014-10-22 AR ARP140103960A patent/AR098145A1/es unknown
- 2014-10-23 UY UY0001035792A patent/UY35792A/es not_active Application Discontinuation
- 2014-10-24 MA MA39054A patent/MA39054B1/fr unknown
- 2014-10-24 TW TW103136873A patent/TWI673268B/zh active
- 2014-10-24 TW TW108124006A patent/TWI690528B/zh active

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2010119284A1 (fr) *	2009-04-15	2010-10-21	Astex Therapeutics Limited	Dérivés hétérocyclyle bicycliques en tant qu'inhibiteurs des fgfr kinases destinés à un usage thérapeutique
WO2013061080A1 (fr) *	2011-10-28	2013-05-02	Astex Therapeutics Limited	Pyridopyrazines anti-cancéreuses par l'inhibition de kinases de fgfr

Also Published As

Publication number	Publication date
TWI690528B (zh)	2020-04-11
MA39054A1 (fr)	2018-02-28
AR098145A1 (es)	2016-05-04
TW201605853A (zh)	2016-02-16
TW201938560A (zh)	2019-10-01
UY35792A (es)	2015-05-29
MA39054B1 (fr)	2018-09-28

Publication	Publication Date	Title
CN105683188B (zh)	2018-02-09	作为fgfr4抑制剂的稠环二环吡啶基衍生物
CN109310690B (zh)	2021-09-07	异喹啉-3-基甲酰胺类及其制备和其用途
JP7023243B2 (ja)	2022-02-21	イソキノリン－３イル－カルボキサミドならびにその調製および使用の方法
KR101921486B1 (ko)	2018-11-26	ＰＡＲＰ억제제인 4Ｈ-피라졸로[1,5-ａ]벤즈이미다졸 화합물의 아날로그
EP3121177B1 (fr)	2018-08-01	Combinaisons d'antagonistes de trpv4
CN104024252B (zh)	2015-08-26	用于治疗肺动脉高压的双环杂环衍生物
TW202136266A (zh)	2021-10-01	Sos1抑制劑
CN113316576A (zh)	2021-08-27	用于治疗癌症的作为HPK1抑制剂的2,3-二氢-1H-吡咯并[3,4-c]吡啶-1-酮衍生物
CA3107365A1 (fr)	2020-02-20	Composes de pyrazine et leurs utilisations
CN112279837B (zh)	2022-08-09	吡嗪化合物和其用途
CN111747954B (zh)	2021-08-24	吡嗪化合物和其用途
TWI673268B (zh)	2019-10-01	作為ｆｇｆｒ４抑制劑之稠環雙環吡啶基衍生物
CN119546604A (zh)	2025-02-28	作为hpk1抑制剂的吡啶并[3,2-d]嘧啶
WO2025215153A1 (fr)	2025-10-16	Inhibiteurs de prmt5
HK40129387A (zh)	2026-03-06	造血前驱细胞激酶1的吡啶酮及嘧啶酮抑制剂
HK40074500A (en)	2023-01-06	Pyrazine compounds and uses thereof
IL325136A (en)	2026-02-01	Pyrazolo-pyrimidinone compounds for use in methods for inhibiting kinase week1 a
CN121311471A (zh)	2026-01-09	异喹啉酮衍生物和4h-喹嗪酮衍生物以及其用于治疗疾病的药物组合物
HK40053093A (en)	2022-01-28	2,3-dihydro-1h-pyrrolo[3,4-c]pyridin-1-one derivatives as hpk1 inhibitors for the treatment of cancer
HK1195068B (en)	2017-04-13	Trpv4 antagonists