MXPA04012860A

MXPA04012860A - Proceso quimico.

Proceso quimico.

Info

Publication number: MXPA04012860A
Authority: MX; Mexico
Prior art keywords: alkyl; formula; compound; hydrogen; methyl
Prior art date: 2002-06-17

Application number

MXPA04012860A

Other languages

English (en)

Spanish (es)

Inventor

Jeffrey Alan Stafford

Original Assignee

Smithkline Beecham Corp

Priority date

2002-06-17

Filing date

2003-06-17

Publication date

2005-09-20

2003-06-17 Application filed by Smithkline Beecham Corp filed Critical Smithkline Beecham Corp

2005-09-20 Publication of MXPA04012860A publication Critical patent/MXPA04012860A/es

Links

238000001311 chemical methods and process Methods 0.000 title description 2
238000000034 method Methods 0.000 claims abstract description 56
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 30
238000011282 treatment Methods 0.000 claims abstract description 24
238000002360 preparation method Methods 0.000 claims abstract description 20
230000008569 process Effects 0.000 claims abstract description 15
201000010099 disease Diseases 0.000 claims abstract description 10
150000003230 pyrimidines Chemical class 0.000 claims abstract description 8
229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 claims abstract description 6
230000003463 hyperproliferative effect Effects 0.000 claims abstract 2
150000001875 compounds Chemical class 0.000 claims description 131
-1 aralkoxy Chemical group 0.000 claims description 62
125000000217 alkyl group Chemical group 0.000 claims description 61
229910052739 hydrogen Inorganic materials 0.000 claims description 51
239000001257 hydrogen Substances 0.000 claims description 47
238000006243 chemical reaction Methods 0.000 claims description 32
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
125000000753 cycloalkyl group Chemical group 0.000 claims description 24
125000001072 heteroaryl group Chemical group 0.000 claims description 21
125000003118 aryl group Chemical group 0.000 claims description 20
229910052736 halogen Chemical group 0.000 claims description 19
150000002367 halogens Chemical group 0.000 claims description 19
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 16
239000003112 inhibitor Substances 0.000 claims description 16
125000003710 aryl alkyl group Chemical group 0.000 claims description 14
229940100198 alkylating agent Drugs 0.000 claims description 13
239000002168 alkylating agent Substances 0.000 claims description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
229910052799 carbon Inorganic materials 0.000 claims description 11
238000004519 manufacturing process Methods 0.000 claims description 11
125000001769 aryl amino group Chemical group 0.000 claims description 8
150000001721 carbon Chemical group 0.000 claims description 7
238000009833 condensation Methods 0.000 claims description 6
230000005494 condensation Effects 0.000 claims description 6
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
150000002431 hydrogen Chemical class 0.000 claims 5
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 2
229940091171 VEGFR-2 tyrosine kinase inhibitor Drugs 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 74
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 65
239000000203 mixture Substances 0.000 description 61
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
235000002639 sodium chloride Nutrition 0.000 description 42
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 41
239000000243 solution Substances 0.000 description 41
150000003839 salts Chemical class 0.000 description 40
239000007787 solid Substances 0.000 description 36
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 35
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
238000005481 NMR spectroscopy Methods 0.000 description 30
239000012453 solvate Substances 0.000 description 30
239000000543 intermediate Substances 0.000 description 29
239000000047 product Substances 0.000 description 29
235000019439 ethyl acetate Nutrition 0.000 description 28
239000002904 solvent Substances 0.000 description 28
230000000694 effects Effects 0.000 description 27
101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 25
238000001819 mass spectrum Methods 0.000 description 25
102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 24
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
239000008194 pharmaceutical composition Substances 0.000 description 22
230000002829 reductive effect Effects 0.000 description 22
208000035475 disorder Diseases 0.000 description 20
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 20
239000011541 reaction mixture Substances 0.000 description 20
229910001868 water Inorganic materials 0.000 description 20
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
206010028980 Neoplasm Diseases 0.000 description 18
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 18
230000033115 angiogenesis Effects 0.000 description 17
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
239000010410 layer Substances 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
201000011510 cancer Diseases 0.000 description 14
238000009472 formulation Methods 0.000 description 14
239000006072 paste Substances 0.000 description 14
239000000843 powder Substances 0.000 description 14
238000003756 stirring Methods 0.000 description 14
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 13
238000001914 filtration Methods 0.000 description 12
239000000725 suspension Substances 0.000 description 12
PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 11
108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 11
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 11
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 11
125000001188 haloalkyl group Chemical group 0.000 description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
241000124008 Mammalia Species 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
238000004128 high performance liquid chromatography Methods 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
125000004432 carbon atom Chemical group C* 0.000 description 9
239000003795 chemical substances by application Substances 0.000 description 9
239000003814 drug Substances 0.000 description 9
229910052757 nitrogen Inorganic materials 0.000 description 9
238000006467 substitution reaction Methods 0.000 description 9
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
108091008605 VEGF receptors Proteins 0.000 description 8
230000002159 abnormal effect Effects 0.000 description 8
239000002246 antineoplastic agent Substances 0.000 description 8
238000010992 reflux Methods 0.000 description 8
238000003786 synthesis reaction Methods 0.000 description 8
239000003826 tablet Substances 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
239000003981 vehicle Substances 0.000 description 8
108091000080 Phosphotransferase Proteins 0.000 description 7
239000004480 active ingredient Substances 0.000 description 7
230000029936 alkylation Effects 0.000 description 7
238000005804 alkylation reaction Methods 0.000 description 7
230000002491 angiogenic effect Effects 0.000 description 7
239000000463 material Substances 0.000 description 7
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
102000020233 phosphotransferase Human genes 0.000 description 7
238000000746 purification Methods 0.000 description 7
125000001424 substituent group Chemical group 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
125000003545 alkoxy group Chemical group 0.000 description 6
125000004647 alkyl sulfenyl group Chemical group 0.000 description 6
125000004390 alkyl sulfonyl group Chemical group 0.000 description 6
125000004414 alkyl thio group Chemical group 0.000 description 6
125000002947 alkylene group Chemical group 0.000 description 6
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 6
229940034982 antineoplastic agent Drugs 0.000 description 6
125000004093 cyano group Chemical group *C#N 0.000 description 6
230000006870 function Effects 0.000 description 6
125000000623 heterocyclic group Chemical group 0.000 description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
125000004043 oxo group Chemical group O=* 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
230000009467 reduction Effects 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
JHGRUPGVUMAQQU-UHFFFAOYSA-N 2,3-dimethyl-6-nitroindazole Chemical compound C1=C([N+]([O-])=O)C=CC2=C(C)N(C)N=C21 JHGRUPGVUMAQQU-UHFFFAOYSA-N 0.000 description 5
102100022014 Angiopoietin-1 receptor Human genes 0.000 description 5
239000004215 Carbon black (E152) Substances 0.000 description 5
102000009465 Growth Factor Receptors Human genes 0.000 description 5
108010009202 Growth Factor Receptors Proteins 0.000 description 5
101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
229920002472 Starch Polymers 0.000 description 5
102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 5
239000002253 acid Substances 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
210000004027 cell Anatomy 0.000 description 5
230000022131 cell cycle Effects 0.000 description 5
239000006071 cream Substances 0.000 description 5
239000006196 drop Substances 0.000 description 5
239000008187 granular material Substances 0.000 description 5
229930195733 hydrocarbon Natural products 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000002609 medium Substances 0.000 description 5
239000003921 oil Substances 0.000 description 5
229910052763 palladium Inorganic materials 0.000 description 5
125000005010 perfluoroalkyl group Chemical group 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
239000008107 starch Substances 0.000 description 5
235000019698 starch Nutrition 0.000 description 5
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 5
229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 5
XJQWZUJNHLGBQG-UHFFFAOYSA-N 1-(methylsulfonylmethyl)-4-nitrobenzene Chemical compound CS(=O)(=O)CC1=CC=C([N+]([O-])=O)C=C1 XJQWZUJNHLGBQG-UHFFFAOYSA-N 0.000 description 4
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 description 4
KTPBKMYOIFHJMI-UHFFFAOYSA-N 5-amino-2-methylbenzenesulfonamide Chemical compound CC1=CC=C(N)C=C1S(N)(=O)=O KTPBKMYOIFHJMI-UHFFFAOYSA-N 0.000 description 4
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
239000011230 binding agent Substances 0.000 description 4
239000002775 capsule Substances 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
239000012065 filter cake Substances 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
239000000314 lubricant Substances 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
230000001404 mediated effect Effects 0.000 description 4
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
239000000546 pharmaceutical excipient Substances 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
229910052717 sulfur Inorganic materials 0.000 description 4
239000011593 sulfur Substances 0.000 description 4
238000012360 testing method Methods 0.000 description 4
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
238000002560 therapeutic procedure Methods 0.000 description 4
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 4
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
PVNVSSNARYHLRF-UHFFFAOYSA-N 2,3-dimethylindazol-6-amine Chemical compound C1=C(N)C=CC2=C(C)N(C)N=C21 PVNVSSNARYHLRF-UHFFFAOYSA-N 0.000 description 3
BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 3
FUNWSYKLFDLUIZ-UHFFFAOYSA-N 3-methyl-6-nitro-2h-indazole Chemical compound C1=C([N+]([O-])=O)C=CC2=C(C)NN=C21 FUNWSYKLFDLUIZ-UHFFFAOYSA-N 0.000 description 3
OWIRCRREDNEXTA-UHFFFAOYSA-N 3-nitro-1h-indazole Chemical class C1=CC=C2C([N+](=O)[O-])=NNC2=C1 OWIRCRREDNEXTA-UHFFFAOYSA-N 0.000 description 3
WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 3
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 3
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 3
108091008794 FGF receptors Proteins 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
230000004913 activation Effects 0.000 description 3
239000013543 active substance Substances 0.000 description 3
125000002252 acyl group Chemical group 0.000 description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
238000011319 anticancer therapy Methods 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
125000003435 aroyl group Chemical group 0.000 description 3
239000012298 atmosphere Substances 0.000 description 3
150000001555 benzenes Chemical group 0.000 description 3
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
229910000024 caesium carbonate Inorganic materials 0.000 description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
238000000576 coating method Methods 0.000 description 3
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 3
239000000975 dye Substances 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
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239000008273 gelatin Substances 0.000 description 3
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235000011852 gelatine desserts Nutrition 0.000 description 3
125000005843 halogen group Chemical group 0.000 description 3
150000002430 hydrocarbons Chemical class 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 3
238000002156 mixing Methods 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
239000012071 phase Substances 0.000 description 3
230000026731 phosphorylation Effects 0.000 description 3
238000006366 phosphorylation reaction Methods 0.000 description 3
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102000054765 polymorphisms of proteins Human genes 0.000 description 3
230000035755 proliferation Effects 0.000 description 3
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
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125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 3
OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 3
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108020003175 receptors Proteins 0.000 description 3
230000004044 response Effects 0.000 description 3
239000011734 sodium Substances 0.000 description 3
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239000011780 sodium chloride Substances 0.000 description 3
235000011150 stannous chloride Nutrition 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
238000011200 topical administration Methods 0.000 description 3
239000001993 wax Substances 0.000 description 3
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
AXZWLBLGYSSPEQ-UHFFFAOYSA-N 1-(2-methylsulfonylpropan-2-yl)-4-nitrobenzene Chemical compound CS(=O)(=O)C(C)(C)C1=CC=C([N+]([O-])=O)C=C1 AXZWLBLGYSSPEQ-UHFFFAOYSA-N 0.000 description 2
VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 2
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 2
SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
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