DE69732780T2 - Pyrimiderivate und verfahren zu ihrer herstellung - Google Patents
Pyrimiderivate und verfahren zu ihrer herstellung Download PDFInfo
- Publication number
- DE69732780T2 DE69732780T2 DE69732780T DE69732780T DE69732780T2 DE 69732780 T2 DE69732780 T2 DE 69732780T2 DE 69732780 T DE69732780 T DE 69732780T DE 69732780 T DE69732780 T DE 69732780T DE 69732780 T2 DE69732780 T2 DE 69732780T2
- Authority
- DE
- Germany
- Prior art keywords
- mmol
- diyl
- pyrimidine
- amino
- pyrazolo
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims description 34
- 238000004519 manufacturing process Methods 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 97
- LHCPRYRLDOSKHK-UHFFFAOYSA-N 7-deaza-8-aza-adenine Chemical class NC1=NC=NC2=C1C=NN2 LHCPRYRLDOSKHK-UHFFFAOYSA-N 0.000 claims abstract 2
- -1 cyano, amino Chemical group 0.000 claims description 253
- 229910052757 nitrogen Inorganic materials 0.000 claims description 50
- 150000003839 salts Chemical class 0.000 claims description 45
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 31
- 125000003282 alkyl amino group Chemical group 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 20
- 239000001301 oxygen Substances 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 206010028980 Neoplasm Diseases 0.000 claims description 18
- 150000003254 radicals Chemical group 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 18
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 230000008569 process Effects 0.000 claims description 16
- 229910052717 sulfur Chemical group 0.000 claims description 16
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 15
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
- 125000006413 ring segment Chemical group 0.000 claims description 14
- 239000011593 sulfur Chemical group 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical group 0.000 claims description 10
- 125000004423 acyloxy group Chemical group 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 239000012453 solvate Substances 0.000 claims description 8
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 7
- 235000019253 formic acid Nutrition 0.000 claims description 7
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 5
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 5
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 239000002841 Lewis acid Substances 0.000 claims description 3
- 125000005281 alkyl ureido group Chemical group 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 150000003948 formamides Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 150000007517 lewis acids Chemical class 0.000 claims description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- UWCMSAAJPUQSML-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-pyridin-3-yl-2h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound ClC1=CC=CC(NC=2C3=C(NC=4C=NC=CC=4)NN=C3N=CN=2)=C1 UWCMSAAJPUQSML-UHFFFAOYSA-N 0.000 claims description 2
- UWXBALRSGLYKKX-UHFFFAOYSA-N [4-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methylurea Chemical compound C1=CC(CNC(=O)N)=CC=C1NC1=C2C(NC=3C=C(Cl)C=CC=3)=NC=NC2=NN1 UWXBALRSGLYKKX-UHFFFAOYSA-N 0.000 claims description 2
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 2
- 238000002512 chemotherapy Methods 0.000 claims 2
- OXNGKCPRVRBHPO-XLMUYGLTSA-N alpha-L-Fucp-(1->2)-beta-D-Galp-(1->3)-[alpha-L-Fucp-(1->4)]-beta-D-GlcpNAc Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@H]2[C@@H]([C@@H](CO)O[C@@H](O)[C@@H]2NC(C)=O)O[C@H]2[C@H]([C@H](O)[C@H](O)[C@H](C)O2)O)O[C@H](CO)[C@H](O)[C@@H]1O OXNGKCPRVRBHPO-XLMUYGLTSA-N 0.000 claims 1
- 230000000259 anti-tumor effect Effects 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 abstract description 10
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 7
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 abstract description 6
- 108091000080 Phosphotransferase Proteins 0.000 abstract description 4
- 102000020233 phosphotransferase Human genes 0.000 abstract description 4
- 239000002246 antineoplastic agent Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 366
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 255
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 176
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 167
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 157
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 127
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
- 239000000203 mixture Substances 0.000 description 101
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 90
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 87
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 87
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 86
- 238000001704 evaporation Methods 0.000 description 78
- 230000008020 evaporation Effects 0.000 description 78
- 239000011541 reaction mixture Substances 0.000 description 77
- 238000004128 high performance liquid chromatography Methods 0.000 description 71
- 239000000243 solution Substances 0.000 description 69
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 61
- 238000001914 filtration Methods 0.000 description 59
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
- 229960000583 acetic acid Drugs 0.000 description 53
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 52
- WVRNRMIYOAEDJT-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-2h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound C=12C(N)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 WVRNRMIYOAEDJT-UHFFFAOYSA-N 0.000 description 48
- 238000003756 stirring Methods 0.000 description 48
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 44
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 43
- 238000006243 chemical reaction Methods 0.000 description 43
- 238000005406 washing Methods 0.000 description 40
- 239000007858 starting material Substances 0.000 description 39
- 235000002639 sodium chloride Nutrition 0.000 description 34
- 238000001816 cooling Methods 0.000 description 31
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 28
- 239000000543 intermediate Substances 0.000 description 28
- 238000010992 reflux Methods 0.000 description 28
- 238000009835 boiling Methods 0.000 description 27
- 239000011734 sodium Substances 0.000 description 27
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- 239000000725 suspension Substances 0.000 description 25
- 238000007792 addition Methods 0.000 description 23
- 238000010626 work up procedure Methods 0.000 description 23
- 239000012267 brine Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000004480 active ingredient Substances 0.000 description 18
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- 230000009467 reduction Effects 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 16
- 238000001953 recrystallisation Methods 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000002253 acid Substances 0.000 description 15
- 238000002425 crystallisation Methods 0.000 description 15
- 230000008025 crystallization Effects 0.000 description 15
- 239000012299 nitrogen atmosphere Substances 0.000 description 15
- VOTCDONNSQKDMG-UHFFFAOYSA-N 3-n-[4-(aminomethyl)phenyl]-4-n-(3-chlorophenyl)-2h-pyrazolo[3,4-d]pyrimidine-3,4-diamine;hydrate Chemical compound O.C1=CC(CN)=CC=C1NC1=C2C(NC=3C=C(Cl)C=CC=3)=NC=NC2=NN1 VOTCDONNSQKDMG-UHFFFAOYSA-N 0.000 description 14
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 14
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 13
- 238000001035 drying Methods 0.000 description 13
- 239000012065 filter cake Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 230000029087 digestion Effects 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 239000008346 aqueous phase Substances 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- 229910004298 SiO 2 Inorganic materials 0.000 description 10
- 239000002775 capsule Substances 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 230000007717 exclusion Effects 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- BWKAYBPLDRWMCJ-UHFFFAOYSA-N 1,1-diethoxy-n,n-dimethylmethanamine Chemical compound CCOC(N(C)C)OCC BWKAYBPLDRWMCJ-UHFFFAOYSA-N 0.000 description 9
- FKOVCGDDQULJSS-UHFFFAOYSA-N 3-n-[3-(aminomethyl)phenyl]-4-n-(3-chlorophenyl)-2h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound NCC1=CC=CC(NC2=C3C(NC=4C=C(Cl)C=CC=4)=NC=NC3=NN2)=C1 FKOVCGDDQULJSS-UHFFFAOYSA-N 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- FICQFRCPSFCFBY-UHFFFAOYSA-N 2-[bis(methylsulfanyl)methylidene]propanedinitrile Chemical compound CSC(SC)=C(C#N)C#N FICQFRCPSFCFBY-UHFFFAOYSA-N 0.000 description 8
- NMGHWHCTRGZZOP-UHFFFAOYSA-N 3-chloroaniline;hydron;chloride Chemical compound Cl.NC1=CC=CC(Cl)=C1 NMGHWHCTRGZZOP-UHFFFAOYSA-N 0.000 description 8
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 125000006308 propyl amino group Chemical group 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- HCFFIHOCFOHSCS-UHFFFAOYSA-N n-(3-chlorophenyl)-3-piperazin-1-yl-1h-pyrazolo[3,4-d]pyrimidin-4-amine;dihydrochloride Chemical compound Cl.Cl.ClC1=CC=CC(NC=2C=3C(N4CCNCC4)=NNC=3N=CN=2)=C1 HCFFIHOCFOHSCS-UHFFFAOYSA-N 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 229920001223 polyethylene glycol Chemical class 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 6
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 6
- 239000002202 Polyethylene glycol Chemical class 0.000 description 6
- 102000001253 Protein Kinase Human genes 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 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
- 238000000354 decomposition reaction Methods 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 108060006633 protein kinase Proteins 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 5
- 102000001301 EGF receptor Human genes 0.000 description 5
- 108060006698 EGF receptor Proteins 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 125000006309 butyl amino group Chemical group 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 229940014800 succinic anhydride Drugs 0.000 description 5
- 239000004474 valine Substances 0.000 description 5
- QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical group C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 description 4
- UDLSPIOZKAXXNP-UHFFFAOYSA-N 2-(2h-tetrazol-5-yl)benzaldehyde Chemical compound O=CC1=CC=CC=C1C1=NN=NN1 UDLSPIOZKAXXNP-UHFFFAOYSA-N 0.000 description 4
- GWZICMAGCVWLAY-UHFFFAOYSA-N 3-(2h-tetrazol-5-yl)benzaldehyde Chemical compound O=CC1=CC=CC(C2=NNN=N2)=C1 GWZICMAGCVWLAY-UHFFFAOYSA-N 0.000 description 4
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 4
- SRGPTCYCHZMFOR-UHFFFAOYSA-N 4-(2h-tetrazol-5-yl)benzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=NN=NN1 SRGPTCYCHZMFOR-UHFFFAOYSA-N 0.000 description 4
- AOKPZEFVROUSHF-UHFFFAOYSA-N 4-N-(3-chlorophenyl)-1H-pyrazole-4,5-diamine Chemical compound N1N=CC(NC=2C=C(Cl)C=CC=2)=C1N AOKPZEFVROUSHF-UHFFFAOYSA-N 0.000 description 4
- 241000208199 Buxus sempervirens Species 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 125000005456 glyceride group Chemical group 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 229940098779 methanesulfonic acid Drugs 0.000 description 4
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 3
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 3
- ZZVZOYDPOMZOET-UHFFFAOYSA-N 3-n-(2-aminoethyl)-4-n-(3-chlorophenyl)-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound C=12C(NCCN)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 ZZVZOYDPOMZOET-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 102100030011 Endoribonuclease Human genes 0.000 description 3
- 101710199605 Endoribonuclease Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 3
- 101800003838 Epidermal growth factor Proteins 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 101710113029 Serine/threonine-protein kinase Proteins 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- AJEHNBIPLQJTNU-UHFFFAOYSA-N cyanomethyl acetate Chemical compound CC(=O)OCC#N AJEHNBIPLQJTNU-UHFFFAOYSA-N 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 229940116977 epidermal growth factor Drugs 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 238000001640 fractional crystallisation Methods 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 150000004677 hydrates Chemical class 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 150000002466 imines Chemical class 0.000 description 3
- 239000011261 inert gas Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- WQEPLUUGTLDZJY-UHFFFAOYSA-N pentadecanoic acid Chemical compound CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 3
- PDVFSPNIEOYOQL-UHFFFAOYSA-N (4-methylphenyl)sulfonyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OS(=O)(=O)C1=CC=C(C)C=C1 PDVFSPNIEOYOQL-UHFFFAOYSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- YGROVARESCMSTE-HNNXBMFYSA-N 1,1-dimethyl-3-[[3-[[4-[[(1s)-1-phenylethyl]amino]-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]urea Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(C=12)=NC=NC2=NNC=1NC1=CC=CC(CNC(=O)N(C)C)=C1 YGROVARESCMSTE-HNNXBMFYSA-N 0.000 description 2
- OUKQTRFCDKSEPL-UHFFFAOYSA-N 1-Methyl-2-pyrrolecarboxaldehyde Chemical compound CN1C=CC=C1C=O OUKQTRFCDKSEPL-UHFFFAOYSA-N 0.000 description 2
- ANEKWLPNAALWIY-UHFFFAOYSA-N 1-benzyl-3-(pyridin-3-ylamino)-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound Oc1ncnc2n(Cc3ccccc3)nc(Nc3cccnc3)c12 ANEKWLPNAALWIY-UHFFFAOYSA-N 0.000 description 2
- JPCDUFBPRKYBPX-UHFFFAOYSA-N 1-benzyl-4-n-(3-chlorophenyl)-3-n-pyridin-3-ylpyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound ClC1=CC=CC(NC=2C=3C(NC=4C=NC=CC=4)=NN(CC=4C=CC=CC=4)C=3N=CN=2)=C1 JPCDUFBPRKYBPX-UHFFFAOYSA-N 0.000 description 2
- TWFNGPDYMFEHOB-UHFFFAOYSA-N 1-bromo-4-(dimethoxymethyl)benzene Chemical compound COC(OC)C1=CC=C(Br)C=C1 TWFNGPDYMFEHOB-UHFFFAOYSA-N 0.000 description 2
- HHIRBXHEYVDUAM-UHFFFAOYSA-N 1-chloro-3-isocyanatobenzene Chemical compound ClC1=CC=CC(N=C=O)=C1 HHIRBXHEYVDUAM-UHFFFAOYSA-N 0.000 description 2
- RBZRMBCLZMEYEH-UHFFFAOYSA-N 1h-pyrazol-1-ium-1-carboximidamide;chloride Chemical compound Cl.NC(=N)N1C=CC=N1 RBZRMBCLZMEYEH-UHFFFAOYSA-N 0.000 description 2
- KEUDMLLLHGLIGH-UHFFFAOYSA-N 1h-pyrazole;pyrimidine Chemical compound C=1C=NNC=1.C1=CN=CN=C1 KEUDMLLLHGLIGH-UHFFFAOYSA-N 0.000 description 2
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 2
- FJJYHTVHBVXEEQ-UHFFFAOYSA-N 2,2-dimethylpropanal Chemical compound CC(C)(C)C=O FJJYHTVHBVXEEQ-UHFFFAOYSA-N 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- YKOKPKDAZDRHDI-UHFFFAOYSA-N 2-(2-methylpropoxycarbonylamino)acetic acid Chemical compound CC(C)COC(=O)NCC(O)=O YKOKPKDAZDRHDI-UHFFFAOYSA-N 0.000 description 2
- MCVVISCDWBZKQQ-UHFFFAOYSA-N 2-(2-methyltetrazol-5-yl)benzaldehyde Chemical compound CN1N=NC(C=2C(=CC=CC=2)C=O)=N1 MCVVISCDWBZKQQ-UHFFFAOYSA-N 0.000 description 2
- PIAMOLBQDIFKIJ-UHFFFAOYSA-N 2-(2-tert-butyltetrazol-5-yl)benzaldehyde Chemical compound CC(C)(C)N1N=NC(C=2C(=CC=CC=2)C=O)=N1 PIAMOLBQDIFKIJ-UHFFFAOYSA-N 0.000 description 2
- OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 description 2
- ROSNJPXJYAQFCN-UHFFFAOYSA-N 2-[methylsulfanyl(morpholin-4-yl)methylidene]propanedinitrile Chemical compound N#CC(C#N)=C(SC)N1CCOCC1 ROSNJPXJYAQFCN-UHFFFAOYSA-N 0.000 description 2
- HIXVLGAPGRNEFN-UHFFFAOYSA-N 2-[methylsulfanyl-(pyridin-3-ylamino)methylidene]propanedinitrile Chemical compound N#CC(C#N)=C(SC)NC1=CC=CN=C1 HIXVLGAPGRNEFN-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- CHMNRJCRDOWYLX-UHFFFAOYSA-N 2h-tetrazol-5-ylmethanol Chemical compound OCC1=NN=NN1 CHMNRJCRDOWYLX-UHFFFAOYSA-N 0.000 description 2
- UTRBWZIEAHEEEB-UHFFFAOYSA-N 2h-tetrazole-5-carbaldehyde Chemical compound O=CC1=NN=NN1 UTRBWZIEAHEEEB-UHFFFAOYSA-N 0.000 description 2
- SJSOFNCYXJUNBT-UHFFFAOYSA-N 3,4,5-trimethoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC(OC)=C1OC SJSOFNCYXJUNBT-UHFFFAOYSA-N 0.000 description 2
- URGXMMSFJZEXDL-UHFFFAOYSA-N 3-(2-methyltetrazol-5-yl)benzaldehyde Chemical compound CN1N=NC(C=2C=C(C=O)C=CC=2)=N1 URGXMMSFJZEXDL-UHFFFAOYSA-N 0.000 description 2
- WPJXYFJPIATWIF-UHFFFAOYSA-N 3-(2-tert-butyltetrazol-5-yl)benzaldehyde Chemical compound CC(C)(C)N1N=NC(C=2C=C(C=O)C=CC=2)=N1 WPJXYFJPIATWIF-UHFFFAOYSA-N 0.000 description 2
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
- CQLLRURGHWMUTE-UHFFFAOYSA-N 3-chloro-4-fluoroaniline;hydrochloride Chemical compound Cl.NC1=CC=C(F)C(Cl)=C1 CQLLRURGHWMUTE-UHFFFAOYSA-N 0.000 description 2
- IKCJACCRTBMTAP-UHFFFAOYSA-N 3-n-(2-aminoethyl)-4-n-(3-chlorophenyl)-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine;dihydrochloride Chemical compound Cl.Cl.C=12C(NCCN)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 IKCJACCRTBMTAP-UHFFFAOYSA-N 0.000 description 2
- BEXPELAOVIOQHQ-UHFFFAOYSA-N 3-n-benzyl-4-n-(3-chlorophenyl)-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound ClC1=CC=CC(NC=2C=3C(NCC=4C=CC=CC=4)=NNC=3N=CN=2)=C1 BEXPELAOVIOQHQ-UHFFFAOYSA-N 0.000 description 2
- LQLBILPEELCFQI-UHFFFAOYSA-N 4-(1,3-thiazol-2-yl)benzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=NC=CS1 LQLBILPEELCFQI-UHFFFAOYSA-N 0.000 description 2
- GDRJJCWOMBAKME-UHFFFAOYSA-N 4-(1,3-thiazol-5-yl)benzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=CN=CS1 GDRJJCWOMBAKME-UHFFFAOYSA-N 0.000 description 2
- WHIFEKRDYLWPBO-UHFFFAOYSA-N 4-(2-methyltetrazol-5-yl)benzaldehyde Chemical compound CN1N=NC(C=2C=CC(C=O)=CC=2)=N1 WHIFEKRDYLWPBO-UHFFFAOYSA-N 0.000 description 2
- NTIULYRWZOCVPS-UHFFFAOYSA-N 4-(2-tert-butyltetrazol-5-yl)benzaldehyde Chemical compound CC(C)(C)N1N=NC(C=2C=CC(C=O)=CC=2)=N1 NTIULYRWZOCVPS-UHFFFAOYSA-N 0.000 description 2
- NMLYGLCBSFKJFI-UHFFFAOYSA-N 4-pyridin-2-ylbenzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=CC=CC=N1 NMLYGLCBSFKJFI-UHFFFAOYSA-N 0.000 description 2
- GJSLIWQSMSAADF-UHFFFAOYSA-N 4-pyridin-3-ylbenzonitrile Chemical compound C1=CC(C#N)=CC=C1C1=CC=CN=C1 GJSLIWQSMSAADF-UHFFFAOYSA-N 0.000 description 2
- FAEOEJIIPHVFLT-UHFFFAOYSA-N 4-pyridin-4-ylbenzonitrile Chemical compound C1=CC(C#N)=CC=C1C1=CC=NC=C1 FAEOEJIIPHVFLT-UHFFFAOYSA-N 0.000 description 2
- RUDBCUPNDNTITO-UHFFFAOYSA-N 5-amino-1-benzyl-3-(pyridin-3-ylamino)pyrazole-4-carbonitrile Chemical compound N=1N(CC=2C=CC=CC=2)C(N)=C(C#N)C=1NC1=CC=CN=C1 RUDBCUPNDNTITO-UHFFFAOYSA-N 0.000 description 2
- GBLMKEBHZNMGPD-UHFFFAOYSA-N 5-amino-3-morpholin-4-yl-1h-pyrazole-4-carbonitrile Chemical compound N#CC1=C(N)NN=C1N1CCOCC1 GBLMKEBHZNMGPD-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 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 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 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 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 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
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- LGDSHSYDSCRFAB-UHFFFAOYSA-N Methyl isothiocyanate Chemical compound CN=C=S LGDSHSYDSCRFAB-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- OKJIRPAQVSHGFK-UHFFFAOYSA-N N-acetylglycine Chemical compound CC(=O)NCC(O)=O OKJIRPAQVSHGFK-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- 108090000315 Protein Kinase C Proteins 0.000 description 2
- 102000003923 Protein Kinase C Human genes 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 238000006136 alcoholysis reaction Methods 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 150000004292 cyclic ethers Chemical class 0.000 description 2
- KVFDZFBHBWTVID-UHFFFAOYSA-N cyclohexanecarbaldehyde Chemical compound O=CC1CCCCC1 KVFDZFBHBWTVID-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 2
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 2
- ZQPPMHVWECSIRJ-MDZDMXLPSA-N elaidic acid Chemical compound CCCCCCCC\C=C\CCCCCCCC(O)=O ZQPPMHVWECSIRJ-MDZDMXLPSA-N 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 150000002334 glycols Chemical class 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- KEMQGTRYUADPNZ-UHFFFAOYSA-N heptadecanoic acid Chemical compound CCCCCCCCCCCCCCCCC(O)=O KEMQGTRYUADPNZ-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- JARKCYVAAOWBJS-UHFFFAOYSA-N hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 150000002429 hydrazines Chemical class 0.000 description 2
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
- 125000002950 monocyclic group Chemical class 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- KYJJYJPPPWBRNV-UHFFFAOYSA-N n'-(4-cyano-3-morpholin-4-yl-1h-pyrazol-5-yl)-n,n-dimethylmethanimidamide Chemical compound N#CC1=C(N=CN(C)C)NN=C1N1CCOCC1 KYJJYJPPPWBRNV-UHFFFAOYSA-N 0.000 description 2
- GDNNDFSSBXCOEW-UHFFFAOYSA-N n'-[3-(benzylamino)-4-cyano-1h-pyrazol-5-yl]-n,n-dimethylmethanimidamide Chemical compound N#CC1=C(N=CN(C)C)NN=C1NCC1=CC=CC=C1 GDNNDFSSBXCOEW-UHFFFAOYSA-N 0.000 description 2
- XTEGVFVZDVNBPF-UHFFFAOYSA-N naphthalene-1,5-disulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-N 0.000 description 2
- BDJRBEYXGGNYIS-UHFFFAOYSA-N nonanedioic acid Chemical compound OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 210000001428 peripheral nervous system Anatomy 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 229940081066 picolinic acid Drugs 0.000 description 2
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- VDVJGIYXDVPQLP-UHFFFAOYSA-N piperonylic acid Chemical compound OC(=O)C1=CC=C2OCOC2=C1 VDVJGIYXDVPQLP-UHFFFAOYSA-N 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- ZSKGQVFRTSEPJT-UHFFFAOYSA-N pyrrole-2-carboxaldehyde Chemical compound O=CC1=CC=CN1 ZSKGQVFRTSEPJT-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 230000008054 signal transmission Effects 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000007901 soft capsule Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical compound OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000002511 suppository base Substances 0.000 description 2
- HAAUAYWHANRJQD-UHFFFAOYSA-N tert-butyl 4-(2,2-dicyano-1-methylsulfanylethenyl)piperazine-1-carboxylate Chemical compound N#CC(C#N)=C(SC)N1CCN(C(=O)OC(C)(C)C)CC1 HAAUAYWHANRJQD-UHFFFAOYSA-N 0.000 description 2
- BFXWREKNLXDGRI-UHFFFAOYSA-N tert-butyl 4-(5-amino-4-cyano-1h-pyrazol-3-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NNC(N)=C1C#N BFXWREKNLXDGRI-UHFFFAOYSA-N 0.000 description 2
- KIQHZSCBAUTARE-UHFFFAOYSA-N tert-butyl n-[2-[(2,2-dicyano-1-methylsulfanylethenyl)amino]ethyl]carbamate Chemical compound N#CC(C#N)=C(SC)NCCNC(=O)OC(C)(C)C KIQHZSCBAUTARE-UHFFFAOYSA-N 0.000 description 2
- TUPQWQQIJNJFBP-UHFFFAOYSA-N tert-butyl n-[2-[(5-amino-4-cyano-1h-pyrazol-3-yl)amino]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCNC1=NNC(N)=C1C#N TUPQWQQIJNJFBP-UHFFFAOYSA-N 0.000 description 2
- MADPUEOTYHUGFS-UHFFFAOYSA-N tert-butyl n-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]carbamate Chemical compound C=12C(NCCNC(=O)OC(C)(C)C)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 MADPUEOTYHUGFS-UHFFFAOYSA-N 0.000 description 2
- JQQMSSSMUHOKCQ-UHFFFAOYSA-N tert-butyl n-[[3-[(2,2-dicyano-1-methylsulfanylethenyl)amino]phenyl]methyl]carbamate Chemical compound N#CC(C#N)=C(SC)NC1=CC=CC(CNC(=O)OC(C)(C)C)=C1 JQQMSSSMUHOKCQ-UHFFFAOYSA-N 0.000 description 2
- WUVLUQZWDZGCDB-UHFFFAOYSA-N tert-butyl n-[[3-[(5-amino-4-cyano-1h-pyrazol-3-yl)amino]phenyl]methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=CC(NC=2C(=C(N)NN=2)C#N)=C1 WUVLUQZWDZGCDB-UHFFFAOYSA-N 0.000 description 2
- VXUGPJVLUQCTRO-UHFFFAOYSA-N tert-butyl n-[[3-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=CC(NC=2C3=C(NC=4C=C(Cl)C=CC=4)N=CN=C3NN=2)=C1 VXUGPJVLUQCTRO-UHFFFAOYSA-N 0.000 description 2
- WXGZWQCBIIDZMZ-UHFFFAOYSA-N tert-butyl n-[[3-[[4-cyano-3-(dimethylaminomethylideneamino)-1h-pyrazol-5-yl]amino]phenyl]methyl]carbamate Chemical compound CN(C)C=NC1=NNC(NC=2C=C(CNC(=O)OC(C)(C)C)C=CC=2)=C1C#N WXGZWQCBIIDZMZ-UHFFFAOYSA-N 0.000 description 2
- IIKUKTIDNVWASO-UHFFFAOYSA-N tert-butyl n-[[4-[(2,2-dicyano-1-methylsulfanylethenyl)amino]phenyl]methyl]carbamate Chemical compound N#CC(C#N)=C(SC)NC1=CC=C(CNC(=O)OC(C)(C)C)C=C1 IIKUKTIDNVWASO-UHFFFAOYSA-N 0.000 description 2
- NXCPPVULROHEDP-UHFFFAOYSA-N tert-butyl n-[[4-[(5-amino-4-cyano-1h-pyrazol-3-yl)amino]phenyl]methyl]carbamate Chemical compound C1=CC(CNC(=O)OC(C)(C)C)=CC=C1NC1=NNC(N)=C1C#N NXCPPVULROHEDP-UHFFFAOYSA-N 0.000 description 2
- NPDBDJFLKKQMCM-UHFFFAOYSA-N tert-butylglycine Chemical compound CC(C)(C)C(N)C(O)=O NPDBDJFLKKQMCM-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- SZHOJFHSIKHZHA-UHFFFAOYSA-N tridecanoic acid Chemical compound CCCCCCCCCCCCC(O)=O SZHOJFHSIKHZHA-UHFFFAOYSA-N 0.000 description 2
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 2
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
- 238000003828 vacuum filtration Methods 0.000 description 2
- 229940100445 wheat starch Drugs 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- ZLCOWUKVVFVVKA-WDSKDSINSA-N (2r)-3-[[(2r)-2-acetamido-2-carboxyethyl]disulfanyl]-2-aminopropanoic acid Chemical compound CC(=O)N[C@H](C(O)=O)CSSC[C@H](N)C(O)=O ZLCOWUKVVFVVKA-WDSKDSINSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- KWMLJOLKUYYJFJ-DIHCEYMBSA-N (2r,3s,4r,5r)-2,3,4,5,6,7-hexahydroxyheptanoic acid Chemical compound OCC(O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-DIHCEYMBSA-N 0.000 description 1
- FHDLNHBWZFXEIV-LBPRGKRZSA-N (2s)-2-amino-n-[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]-3-methylbutanamide Chemical compound C12=C(NC(=O)[C@@H](N)C(C)C)NN=C2N=CN=C1NC1=CC=CC(Cl)=C1 FHDLNHBWZFXEIV-LBPRGKRZSA-N 0.000 description 1
- BLANJXVKWGPUKZ-LBPRGKRZSA-N (2s)-2-amino-n-[[3-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]propanamide Chemical compound C[C@H](N)C(=O)NCC1=CC=CC(NC2=C3C(NC=4C=C(Cl)C=CC=4)=NC=NC3=NN2)=C1 BLANJXVKWGPUKZ-LBPRGKRZSA-N 0.000 description 1
- VKHMMYSOMVEQDQ-LBPRGKRZSA-N (2s)-2-amino-n-[[4-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]propanamide Chemical compound C1=CC(CNC(=O)[C@@H](N)C)=CC=C1NC1=C2C(NC=3C=C(Cl)C=CC=3)=NC=NC2=NN1 VKHMMYSOMVEQDQ-LBPRGKRZSA-N 0.000 description 1
- IEKJCNCMDNKWNY-SFHVURJKSA-N (2s)-n-[[4-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]pyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC(NC=2C3=C(NC=4C=CC(CNC(=O)[C@H]5NCCC5)=CC=4)NN=C3N=CN=2)=C1 IEKJCNCMDNKWNY-SFHVURJKSA-N 0.000 description 1
- RBORURQQJIQWBS-QVRNUERCSA-N (4ar,6r,7r,7as)-6-(6-amino-8-bromopurin-9-yl)-2-hydroxy-2-sulfanylidene-4a,6,7,7a-tetrahydro-4h-furo[3,2-d][1,3,2]dioxaphosphinin-7-ol Chemical compound C([C@H]1O2)OP(O)(=S)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1Br RBORURQQJIQWBS-QVRNUERCSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- AFENDNXGAFYKQO-VKHMYHEASA-N (S)-2-hydroxybutyric acid Chemical compound CC[C@H](O)C(O)=O AFENDNXGAFYKQO-VKHMYHEASA-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
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- YGROVARESCMSTE-OAHLLOKOSA-N 1,1-dimethyl-3-[[3-[[4-[[(1r)-1-phenylethyl]amino]-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]urea Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=12)=NC=NC2=NNC=1NC1=CC=CC(CNC(=O)N(C)C)=C1 YGROVARESCMSTE-OAHLLOKOSA-N 0.000 description 1
- TWKGDQIGZQWANP-OAHLLOKOSA-N 1,1-dimethyl-3-[[4-[[4-[[(1r)-1-phenylethyl]amino]-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]urea Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=12)=NC=NC2=NNC=1NC1=CC=C(CNC(=O)N(C)C)C=C1 TWKGDQIGZQWANP-OAHLLOKOSA-N 0.000 description 1
- TWKGDQIGZQWANP-HNNXBMFYSA-N 1,1-dimethyl-3-[[4-[[4-[[(1s)-1-phenylethyl]amino]-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]urea Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(C=12)=NC=NC2=NNC=1NC1=CC=C(CNC(=O)N(C)C)C=C1 TWKGDQIGZQWANP-HNNXBMFYSA-N 0.000 description 1
- DBUAYOWCIUQXQW-UHFFFAOYSA-N 1,3-benzodioxole-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1OCO2 DBUAYOWCIUQXQW-UHFFFAOYSA-N 0.000 description 1
- ZGTFNNUASMWGTM-UHFFFAOYSA-N 1,3-thiazole-2-carbaldehyde Chemical compound O=CC1=NC=CS1 ZGTFNNUASMWGTM-UHFFFAOYSA-N 0.000 description 1
- FMQQJTDTPJPLJL-UHFFFAOYSA-N 1-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]-3-(3-chlorophenyl)urea Chemical compound ClC1=CC=CC(NC(=O)NCCNC=2C3=C(NC=4C=C(Cl)C=CC=4)N=CN=C3NN=2)=C1 FMQQJTDTPJPLJL-UHFFFAOYSA-N 0.000 description 1
- MUJFEFCCYNVTRU-UHFFFAOYSA-N 1-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]-3-(4-chlorophenyl)urea Chemical compound C1=CC(Cl)=CC=C1NC(=O)NCCNC1=NNC2=NC=NC(NC=3C=C(Cl)C=CC=3)=C12 MUJFEFCCYNVTRU-UHFFFAOYSA-N 0.000 description 1
- HUDYMKQAAGGFLT-UHFFFAOYSA-N 1-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]-3-ethylurea Chemical compound C=12C(NCCNC(=O)NCC)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 HUDYMKQAAGGFLT-UHFFFAOYSA-N 0.000 description 1
- QIORYNXHEOOSJV-UHFFFAOYSA-N 1-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]-3-phenylurea Chemical compound ClC1=CC=CC(NC=2C=3C(NCCNC(=O)NC=4C=CC=CC=4)=NNC=3N=CN=2)=C1 QIORYNXHEOOSJV-UHFFFAOYSA-N 0.000 description 1
- BUNRNQIFNIVFKZ-UHFFFAOYSA-N 1-[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]-3-(3-chlorophenyl)urea Chemical compound ClC1=CC=CC(NC(=O)NC2=C3C(NC=4C=C(Cl)C=CC=4)=NC=NC3=NN2)=C1 BUNRNQIFNIVFKZ-UHFFFAOYSA-N 0.000 description 1
- NFRQCKLZWDBFLQ-UHFFFAOYSA-N 1-[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]-3-hexylurea Chemical compound C12=C(NC(=O)NCCCCCC)NN=C2N=CN=C1NC1=CC=CC(Cl)=C1 NFRQCKLZWDBFLQ-UHFFFAOYSA-N 0.000 description 1
- CVVSZWYODIXPQQ-UHFFFAOYSA-N 1-[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]-3-naphthalen-1-ylurea Chemical compound ClC1=CC=CC(NC=2C3=C(NC(=O)NC=4C5=CC=CC=C5C=CC=4)NN=C3N=CN=2)=C1 CVVSZWYODIXPQQ-UHFFFAOYSA-N 0.000 description 1
- PSTIEGMFDZTRMV-UHFFFAOYSA-N 1-[4-[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]piperazin-1-yl]-2,2-dimethylpropan-1-one Chemical compound C1CN(C(=O)C(C)(C)C)CCN1C1=NNC2=NC=NC(NC=3C=C(Cl)C=CC=3)=C12 PSTIEGMFDZTRMV-UHFFFAOYSA-N 0.000 description 1
- JZBZKFBJRFABAH-UHFFFAOYSA-N 1-[4-[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]piperazin-1-yl]propan-1-one Chemical compound C1CN(C(=O)CC)CCN1C1=NNC2=NC=NC(NC=3C=C(Cl)C=CC=3)=C12 JZBZKFBJRFABAH-UHFFFAOYSA-N 0.000 description 1
- DNDRTWYSGYFJDE-UHFFFAOYSA-N 1-[4-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]butyl]-3-ethylurea Chemical compound C=12C(NCCCCNC(=O)NCC)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 DNDRTWYSGYFJDE-UHFFFAOYSA-N 0.000 description 1
- LLABBNFWXSWQPH-UHFFFAOYSA-N 1-[4-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]butyl]-3-phenylurea Chemical compound ClC1=CC=CC(NC=2C=3C(NCCCCNC(=O)NC=4C=CC=CC=4)=NNC=3N=CN=2)=C1 LLABBNFWXSWQPH-UHFFFAOYSA-N 0.000 description 1
- KJENNMJARNXPPX-UHFFFAOYSA-N 1-[[4-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]-3-(3-methoxyphenyl)urea Chemical compound COC1=CC=CC(NC(=O)NCC=2C=CC(NC3=C4C(NC=5C=C(Cl)C=CC=5)=NC=NC4=NN3)=CC=2)=C1 KJENNMJARNXPPX-UHFFFAOYSA-N 0.000 description 1
- GGZYCRZYJPFTEE-UHFFFAOYSA-N 1-[[4-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]-3-ethylurea Chemical compound C1=CC(CNC(=O)NCC)=CC=C1NC1=C2C(NC=3C=C(Cl)C=CC=3)=NC=NC2=NN1 GGZYCRZYJPFTEE-UHFFFAOYSA-N 0.000 description 1
- GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 description 1
- YURDCOUBUCLAGY-UHFFFAOYSA-N 1-benzyl-3-[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]urea Chemical compound ClC1=CC=CC(NC=2C3=C(NC(=O)NCC=4C=CC=CC=4)NN=C3N=CN=2)=C1 YURDCOUBUCLAGY-UHFFFAOYSA-N 0.000 description 1
- NPOVTGVGOBJZPY-UHFFFAOYSA-N 1-isocyanato-3-methoxybenzene Chemical compound COC1=CC=CC(N=C=O)=C1 NPOVTGVGOBJZPY-UHFFFAOYSA-N 0.000 description 1
- BDQNKCYCTYYMAA-UHFFFAOYSA-N 1-isocyanatonaphthalene Chemical compound C1=CC=C2C(N=C=O)=CC=CC2=C1 BDQNKCYCTYYMAA-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 1
- ZQEXIXXJFSQPNA-UHFFFAOYSA-N 1h-imidazole-5-carbaldehyde Chemical compound O=CC1=CNC=N1 ZQEXIXXJFSQPNA-UHFFFAOYSA-N 0.000 description 1
- PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-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
- BEHXDZFQPXYJGA-UHFFFAOYSA-N 2-[(benzylamino)-methylsulfanylmethylidene]propanedinitrile Chemical compound N#CC(C#N)=C(SC)NCC1=CC=CC=C1 BEHXDZFQPXYJGA-UHFFFAOYSA-N 0.000 description 1
- QFFUIIUTUBIVTC-UHFFFAOYSA-N 2-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]guanidine;hydrochloride Chemical compound Cl.C=12C(NCCN=C(N)N)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 QFFUIIUTUBIVTC-UHFFFAOYSA-N 0.000 description 1
- PJIKKPYBFQNFQC-UHFFFAOYSA-N 2-[3-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]propyl]guanidine Chemical compound C=12C(NCCCN=C(N)N)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 PJIKKPYBFQNFQC-UHFFFAOYSA-N 0.000 description 1
- AEJDGWUAZKJQEJ-UHFFFAOYSA-N 2-[4-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]butyl]guanidine Chemical compound C=12C(NCCCCN=C(N)N)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 AEJDGWUAZKJQEJ-UHFFFAOYSA-N 0.000 description 1
- PDIGPPCXUUGYOS-UHFFFAOYSA-N 2-[[3-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]guanidine Chemical compound NC(N)=NCC1=CC=CC(NC2=C3C(NC=4C=C(Cl)C=CC=4)=NC=NC3=NN2)=C1 PDIGPPCXUUGYOS-UHFFFAOYSA-N 0.000 description 1
- YZRMZVPIMIGPLG-UHFFFAOYSA-N 2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethylurea Chemical compound C=12C(NCCNC(=O)N)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 YZRMZVPIMIGPLG-UHFFFAOYSA-N 0.000 description 1
- SYPSWKOGDBPFSU-UHFFFAOYSA-N 2-[[4-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]guanidine;hydrochloride Chemical compound Cl.C1=CC(CN=C(N)N)=CC=C1NC1=C2C(NC=3C=C(Cl)C=CC=3)=NC=NC2=NN1 SYPSWKOGDBPFSU-UHFFFAOYSA-N 0.000 description 1
- OCEVXXWTLWTOPB-UHFFFAOYSA-N 2-[[4-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]isoindole-1,3-dione Chemical compound ClC1=CC=CC(NC=2C3=C(NC=4C=CC(CN5C(C6=CC=CC=C6C5=O)=O)=CC=4)NN=C3N=CN=2)=C1 OCEVXXWTLWTOPB-UHFFFAOYSA-N 0.000 description 1
- UUPBBAJXBWJKKD-UHFFFAOYSA-N 2-amino-n-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]acetamide Chemical compound C=12C(NCCNC(=O)CN)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 UUPBBAJXBWJKKD-UHFFFAOYSA-N 0.000 description 1
- CKSQEYJWASOOFC-UHFFFAOYSA-N 2-amino-n-[3-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]propyl]acetamide Chemical compound C=12C(NCCCNC(=O)CN)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 CKSQEYJWASOOFC-UHFFFAOYSA-N 0.000 description 1
- SCTJWGPLHUKLTR-UHFFFAOYSA-N 2-amino-n-[4-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]butyl]acetamide Chemical compound C=12C(NCCCCNC(=O)CN)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 SCTJWGPLHUKLTR-UHFFFAOYSA-N 0.000 description 1
- JVKMMNSDCVURNY-UHFFFAOYSA-N 2-amino-n-[[3-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]acetamide Chemical compound NCC(=O)NCC1=CC=CC(NC2=C3C(NC=4C=C(Cl)C=CC=4)=NC=NC3=NN2)=C1 JVKMMNSDCVURNY-UHFFFAOYSA-N 0.000 description 1
- CFBIDKXSTJRJFV-UHFFFAOYSA-N 2-amino-n-[[4-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]acetamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.C1=CC(CNC(=O)CN)=CC=C1NC1=C2C(NC=3C=C(Cl)C=CC=3)=NC=NC2=NN1 CFBIDKXSTJRJFV-UHFFFAOYSA-N 0.000 description 1
- RXNZFHIEDZEUQM-UHFFFAOYSA-N 2-bromo-1,3-thiazole Chemical compound BrC1=NC=CS1 RXNZFHIEDZEUQM-UHFFFAOYSA-N 0.000 description 1
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
- QVTPWONEVZJCCS-UHFFFAOYSA-N 2-formylbenzonitrile Chemical compound O=CC1=CC=CC=C1C#N QVTPWONEVZJCCS-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
- OFTKFKYVSBNYEC-UHFFFAOYSA-N 2-furoyl chloride Chemical compound ClC(=O)C1=CC=CO1 OFTKFKYVSBNYEC-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- NEENFROGTJBVNI-UHFFFAOYSA-N 2-methylpropyl n-[2-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]-2-oxoethyl]carbamate Chemical compound C12=C(NC(=O)CNC(=O)OCC(C)C)NN=C2N=CN=C1NC1=CC=CC(Cl)=C1 NEENFROGTJBVNI-UHFFFAOYSA-N 0.000 description 1
- PKRSYEPBQPFNRB-UHFFFAOYSA-N 2-phenoxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1OC1=CC=CC=C1 PKRSYEPBQPFNRB-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- VARLFARZJAEUJS-UHFFFAOYSA-N 2-tert-butyltetrazole Chemical compound CC(C)(C)N1N=CN=N1 VARLFARZJAEUJS-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- IWPZKOJSYQZABD-UHFFFAOYSA-N 3,4,5-trimethoxybenzoic acid Natural products COC1=CC(OC)=CC(C(O)=O)=C1 IWPZKOJSYQZABD-UHFFFAOYSA-N 0.000 description 1
- WVXQJCKMPPMFSU-UHFFFAOYSA-N 3-[[2-(2-tert-butyltetrazol-5-yl)phenyl]methylideneamino]-n-(3-chlorophenyl)-2h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound CC(C)(C)N1N=NC(C=2C(=CC=CC=2)C=NC2=C3C(NC=4C=C(Cl)C=CC=4)=NC=NC3=NN2)=N1 WVXQJCKMPPMFSU-UHFFFAOYSA-N 0.000 description 1
- RTBHFLQDNQRVOD-UHFFFAOYSA-N 3-[[3-(2-tert-butyltetrazol-5-yl)phenyl]methylideneamino]-n-(3-chlorophenyl)-2h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound CC(C)(C)N1N=NC(C=2C=C(C=NC3=C4C(NC=5C=C(Cl)C=CC=5)=NC=NC4=NN3)C=CC=2)=N1 RTBHFLQDNQRVOD-UHFFFAOYSA-N 0.000 description 1
- XRHRUMYOXHNBFA-UHFFFAOYSA-N 3-amino-n-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]benzamide Chemical compound NC1=CC=CC(C(=O)NCCNC=2C3=C(NC=4C=C(Cl)C=CC=4)N=CN=C3NN=2)=C1 XRHRUMYOXHNBFA-UHFFFAOYSA-N 0.000 description 1
- YSEMCVGMNUUNRK-UHFFFAOYSA-N 3-chloro-4-fluoroaniline Chemical compound NC1=CC=C(F)C(Cl)=C1 YSEMCVGMNUUNRK-UHFFFAOYSA-N 0.000 description 1
- HGZJJKZPPMFIBU-UHFFFAOYSA-N 3-formylbenzonitrile Chemical compound O=CC1=CC=CC(C#N)=C1 HGZJJKZPPMFIBU-UHFFFAOYSA-N 0.000 description 1
- RBIGKSZIQCTIJF-UHFFFAOYSA-N 3-formylthiophene Chemical compound O=CC=1C=CSC=1 RBIGKSZIQCTIJF-UHFFFAOYSA-N 0.000 description 1
- AZVSIHIBYRHSLB-UHFFFAOYSA-N 3-furaldehyde Chemical compound O=CC=1C=COC=1 AZVSIHIBYRHSLB-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- JDQDSEVNMTYMOC-UHFFFAOYSA-N 3-methylbenzenesulfonic acid Chemical compound CC1=CC=CC(S(O)(=O)=O)=C1 JDQDSEVNMTYMOC-UHFFFAOYSA-N 0.000 description 1
- QWMCJBXZAIDGPA-UHFFFAOYSA-N 3-n-(3-aminopropyl)-4-n-(3-chlorophenyl)-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine;dihydrochloride Chemical compound Cl.Cl.C=12C(NCCCN)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 QWMCJBXZAIDGPA-UHFFFAOYSA-N 0.000 description 1
- DXQQNZGRQOJXTI-UHFFFAOYSA-N 3-n-(4-aminobutyl)-4-n-(3-chlorophenyl)-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine;dihydrochloride Chemical compound Cl.Cl.C=12C(NCCCCN)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 DXQQNZGRQOJXTI-UHFFFAOYSA-N 0.000 description 1
- XJDQSAYWBRBWSM-UHFFFAOYSA-N 3-n-[4-(aminomethyl)phenyl]-4-n-(3-chlorophenyl)-2h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound C1=CC(CN)=CC=C1NC1=C2C(NC=3C=C(Cl)C=CC=3)=NC=NC2=NN1 XJDQSAYWBRBWSM-UHFFFAOYSA-N 0.000 description 1
- NVWCIJHHHVIHJJ-UHFFFAOYSA-N 3-n-[[2-(2-tert-butyltetrazol-5-yl)phenyl]methyl]-4-n-(3-chlorophenyl)-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound CC(C)(C)N1N=NC(C=2C(=CC=CC=2)CNC=2C3=C(NC=4C=C(Cl)C=CC=4)N=CN=C3NN=2)=N1 NVWCIJHHHVIHJJ-UHFFFAOYSA-N 0.000 description 1
- GAHTVTYAJYAUNY-UHFFFAOYSA-N 3-n-[[3-(2-tert-butyltetrazol-5-yl)phenyl]methyl]-4-n-(3-chlorophenyl)-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound CC(C)(C)N1N=NC(C=2C=C(CNC=3C4=C(NC=5C=C(Cl)C=CC=5)N=CN=C4NN=3)C=CC=2)=N1 GAHTVTYAJYAUNY-UHFFFAOYSA-N 0.000 description 1
- OSJPPGNTCRNQQC-UHFFFAOYSA-N 3-phosphoglyceric acid Chemical compound OC(=O)C(O)COP(O)(O)=O OSJPPGNTCRNQQC-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- MAABALLMMOCVIT-UHFFFAOYSA-N 4-N-(3-chlorophenyl)-3-N-(naphthalen-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound ClC1=CC=CC(NC=2C=3C(NCC=4C=C5C=CC=CC5=CC=4)=NNC=3N=CN=2)=C1 MAABALLMMOCVIT-UHFFFAOYSA-N 0.000 description 1
- BVZCJAJXGKPIGP-UHFFFAOYSA-N 4-amino-n-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]benzamide Chemical compound C1=CC(N)=CC=C1C(=O)NCCNC1=NNC2=NC=NC(NC=3C=C(Cl)C=CC=3)=C12 BVZCJAJXGKPIGP-UHFFFAOYSA-N 0.000 description 1
- YBAZINRZQSAIAY-UHFFFAOYSA-N 4-aminobenzonitrile Chemical compound NC1=CC=C(C#N)C=C1 YBAZINRZQSAIAY-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- FTZJLXIATZSKIL-UHFFFAOYSA-N 4-chloro-1-isocyanato-2-methylbenzene Chemical compound CC1=CC(Cl)=CC=C1N=C=O FTZJLXIATZSKIL-UHFFFAOYSA-N 0.000 description 1
- WZWIQYMTQZCSKI-UHFFFAOYSA-N 4-cyanobenzaldehyde Chemical compound O=CC1=CC=C(C#N)C=C1 WZWIQYMTQZCSKI-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- FXZRYWPXQHLCSX-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-(2,2-dimethylpropyl)-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound C=12C(NCC(C)(C)C)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 FXZRYWPXQHLCSX-UHFFFAOYSA-N 0.000 description 1
- UJAYISLUHGFBEN-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-(pyridin-3-ylmethyl)-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound ClC1=CC=CC(NC=2C=3C(NCC=4C=NC=CC=4)=NNC=3N=CN=2)=C1 UJAYISLUHGFBEN-UHFFFAOYSA-N 0.000 description 1
- SIVUZHNSWQXNPW-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-[(3-phenoxyphenyl)methyl]-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound ClC1=CC=CC(NC=2C=3C(NCC=4C=C(OC=5C=CC=CC=5)C=CC=4)=NNC=3N=CN=2)=C1 SIVUZHNSWQXNPW-UHFFFAOYSA-N 0.000 description 1
- VOMPPMDRXCPJQD-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-[(4-phenylphenyl)methyl]-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound ClC1=CC=CC(NC=2C=3C(NCC=4C=CC(=CC=4)C=4C=CC=CC=4)=NNC=3N=CN=2)=C1 VOMPPMDRXCPJQD-UHFFFAOYSA-N 0.000 description 1
- PPGLWIDOMHZKMF-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-[(4-pyridin-2-ylphenyl)methyl]-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound ClC1=CC=CC(NC=2C=3C(NCC=4C=CC(=CC=4)C=4N=CC=CC=4)=NNC=3N=CN=2)=C1 PPGLWIDOMHZKMF-UHFFFAOYSA-N 0.000 description 1
- FXSJGZQARXVDPF-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-[(4-pyridin-4-ylphenyl)methyl]-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound ClC1=CC=CC(NC=2C=3C(NCC=4C=CC(=CC=4)C=4C=CN=CC=4)=NNC=3N=CN=2)=C1 FXSJGZQARXVDPF-UHFFFAOYSA-N 0.000 description 1
- KPWSWMZPDXQJHR-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-[3-[dimethylamino-(methylideneamino)methyl]phenyl]-2h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound CN(C)C(N=C)C1=CC=CC(NC2=C3C(NC=4C=C(Cl)C=CC=4)=NC=NC3=NN2)=C1 KPWSWMZPDXQJHR-UHFFFAOYSA-N 0.000 description 1
- UENGERUXDFFXDE-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-[[2-(2-methyltetrazol-5-yl)phenyl]methyl]-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound CN1N=NC(C=2C(=CC=CC=2)CNC=2C3=C(NC=4C=C(Cl)C=CC=4)N=CN=C3NN=2)=N1 UENGERUXDFFXDE-UHFFFAOYSA-N 0.000 description 1
- FDTPXXUKUJJXPP-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-[[2-(2h-tetrazol-5-yl)phenyl]methyl]-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound ClC1=CC=CC(NC=2C=3C(NCC=4C(=CC=CC=4)C4=NNN=N4)=NNC=3N=CN=2)=C1 FDTPXXUKUJJXPP-UHFFFAOYSA-N 0.000 description 1
- SICBHVUTHCFQPC-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-[[3-(2-methyltetrazol-5-yl)phenyl]methyl]-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound CN1N=NC(C=2C=C(CNC=3C4=C(NC=5C=C(Cl)C=CC=5)N=CN=C4NN=3)C=CC=2)=N1 SICBHVUTHCFQPC-UHFFFAOYSA-N 0.000 description 1
- WQTLNJPBSBGWDE-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-[[3-(2h-tetrazol-5-yl)phenyl]methyl]-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound ClC1=CC=CC(NC=2C=3C(NCC=4C=C(C=CC=4)C4=NNN=N4)=NNC=3N=CN=2)=C1 WQTLNJPBSBGWDE-UHFFFAOYSA-N 0.000 description 1
- CXJRZNNGNNDHJJ-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-[[4-(1,3-thiazol-5-yl)phenyl]methyl]-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound ClC1=CC=CC(NC=2C=3C(NCC=4C=CC(=CC=4)C=4SC=NC=4)=NNC=3N=CN=2)=C1 CXJRZNNGNNDHJJ-UHFFFAOYSA-N 0.000 description 1
- CNMAOMJSOVSKFI-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-[[4-(2-methyltetrazol-5-yl)phenyl]methyl]-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound CN1N=NC(C=2C=CC(CNC=3C4=C(NC=5C=C(Cl)C=CC=5)N=CN=C4NN=3)=CC=2)=N1 CNMAOMJSOVSKFI-UHFFFAOYSA-N 0.000 description 1
- LDKRZJMFUPGGJS-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-[[4-(2h-tetrazol-5-yl)phenyl]methyl]-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound ClC1=CC=CC(NC=2C=3C(NCC=4C=CC(=CC=4)C4=NNN=N4)=NNC=3N=CN=2)=C1 LDKRZJMFUPGGJS-UHFFFAOYSA-N 0.000 description 1
- YMRJKWWMQFVYRA-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-cyclohexyl-3-n-methyl-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound N=1NC2=NC=NC(NC=3C=C(Cl)C=CC=3)=C2C=1N(C)C1CCCCC1 YMRJKWWMQFVYRA-UHFFFAOYSA-N 0.000 description 1
- KZGBOSJEZDQTCI-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-hexyl-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound C=12C(NCCCCCC)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 KZGBOSJEZDQTCI-UHFFFAOYSA-N 0.000 description 1
- SXSHNSQZDNIPCS-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-methyl-3-n-(1h-pyrrol-2-yl)-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound N=1NC2=NC=NC(NC=3C=C(Cl)C=CC=3)=C2C=1N(C)C1=CC=CN1 SXSHNSQZDNIPCS-UHFFFAOYSA-N 0.000 description 1
- SHXYTAPAPBINCH-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-methyl-3-n-pyridin-2-yl-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound C=1C=CC=NC=1N(C)C(C=12)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 SHXYTAPAPBINCH-UHFFFAOYSA-N 0.000 description 1
- KPSIKXIGQBZKAQ-UHFFFAOYSA-N 4-n-(3-chlorophenyl)-3-n-pyridin-4-yl-2h-pyrazolo[3,4-d]pyrimidine-3,4-diamine;hydrochloride Chemical compound Cl.ClC1=CC=CC(NC=2C3=C(NC=4C=CN=CC=4)NN=C3N=CN=2)=C1 KPSIKXIGQBZKAQ-UHFFFAOYSA-N 0.000 description 1
- ISDBWOPVZKNQDW-UHFFFAOYSA-N 4-phenylbenzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=CC=CC=C1 ISDBWOPVZKNQDW-UHFFFAOYSA-N 0.000 description 1
- CCMRFUCSFRRPNT-UHFFFAOYSA-N 4-pyridin-2-ylbenzonitrile Chemical compound C1=CC(C#N)=CC=C1C1=CC=CC=N1 CCMRFUCSFRRPNT-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- MPGNHHYKMGFHSQ-UHFFFAOYSA-N 5-amino-3-(benzylamino)-1h-pyrazole-4-carbonitrile Chemical compound N#CC1=C(N)NN=C1NCC1=CC=CC=C1 MPGNHHYKMGFHSQ-UHFFFAOYSA-N 0.000 description 1
- JBNUSOOHKCOHCX-UHFFFAOYSA-N 5-amino-5-[4-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]-4-oxopentanoic acid Chemical compound C1=CC(C(C(=O)CCC(O)=O)N)=CC=C1NC1=C2C(NC=3C=C(Cl)C=CC=3)=NC=NC2=NN1 JBNUSOOHKCOHCX-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- AHISYUZBWDSPQL-UHFFFAOYSA-N 6-methylpyridine-2-carbaldehyde Chemical compound CC1=CC=CC(C=O)=N1 AHISYUZBWDSPQL-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- WDJHALXBUFZDSR-UHFFFAOYSA-N Acetoacetic acid Natural products CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 1
- 241001136792 Alle Species 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 238000011729 BALB/c nude mouse Methods 0.000 description 1
- 235000021357 Behenic acid Nutrition 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- FUEPYXHIAQKOSZ-UHFFFAOYSA-N CS(=O)(=O)C(=C(C#N)C#N)S(=O)(=O)C Chemical compound CS(=O)(=O)C(=C(C#N)C#N)S(=O)(=O)C FUEPYXHIAQKOSZ-UHFFFAOYSA-N 0.000 description 1
- 102000029330 CSK Tyrosine-Protein Kinase Human genes 0.000 description 1
- 108010069682 CSK Tyrosine-Protein Kinase Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- GGCIVKWBJKDULZ-UHFFFAOYSA-N ClC=1C=C(C=CC=1)NC1=C2C(=NC=N1)NN=C2NC(=O)NCC=1C=NC=CC=1 Chemical compound ClC=1C=C(C=CC=1)NC1=C2C(=NC=N1)NN=C2NC(=O)NCC=1C=NC=CC=1 GGCIVKWBJKDULZ-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- AEMOLEFTQBMNLQ-YMDCURPLSA-N D-galactopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-YMDCURPLSA-N 0.000 description 1
- DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Natural products CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 1
- 238000006088 Dimroth rearrangement reaction Methods 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- KIWBPDUYBMNFTB-UHFFFAOYSA-N Ethyl hydrogen sulfate Chemical compound CCOS(O)(=O)=O KIWBPDUYBMNFTB-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102100026720 Interferon beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001024304 Mino Species 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- UOUWJXOVEKKWJP-UHFFFAOYSA-N N-(3-chlorophenyl)-3-(2H-tetrazol-5-ylmethylideneamino)-2H-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound ClC=1C=C(C=CC1)NC1=C2C(=NC=N1)NN=C2N=CC2=NN=NN2 UOUWJXOVEKKWJP-UHFFFAOYSA-N 0.000 description 1
- MYHHBTRSELUENU-UHFFFAOYSA-N N-[4-(3-chloroanilino)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-1-phenylmethanesulfonamide Chemical compound ClC=1C=C(C=CC=1)NC1=C2C(=NC=N1)NN=C2NS(=O)(=O)CC1=CC=CC=C1 MYHHBTRSELUENU-UHFFFAOYSA-N 0.000 description 1
- HXFOXFJUNFFYMO-BYPYZUCNSA-N N-alpha-acetyl-L-asparagine Chemical compound CC(=O)N[C@H](C(O)=O)CC(N)=O HXFOXFJUNFFYMO-BYPYZUCNSA-N 0.000 description 1
- 208000003788 Neoplasm Micrometastasis Diseases 0.000 description 1
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoryl-L-serine Natural products OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 102000038012 SFKs Human genes 0.000 description 1
- 108091008118 SFKs Proteins 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 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
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- SMEGJBVQLJJKKX-HOTMZDKISA-N [(2R,3S,4S,5R,6R)-5-acetyloxy-3,4,6-trihydroxyoxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@@H](O1)O)OC(=O)C)O)O SMEGJBVQLJJKKX-HOTMZDKISA-N 0.000 description 1
- RYGSWECQIBONLJ-UHFFFAOYSA-N [3-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methylurea Chemical compound NC(=O)NCC1=CC=CC(NC2=C3C(NC=4C=C(Cl)C=CC=4)=NC=NC3=NN2)=C1 RYGSWECQIBONLJ-UHFFFAOYSA-N 0.000 description 1
- KVRXRNISDRQOJT-UHFFFAOYSA-N [4-[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]piperazin-1-yl]-phenylmethanone Chemical compound ClC1=CC=CC(NC=2C=3C(N4CCN(CC4)C(=O)C=4C=CC=CC=4)=NNC=3N=CN=2)=C1 KVRXRNISDRQOJT-UHFFFAOYSA-N 0.000 description 1
- XQAXGZLFSSPBMK-UHFFFAOYSA-M [7-(dimethylamino)phenothiazin-3-ylidene]-dimethylazanium;chloride;trihydrate Chemical compound O.O.O.[Cl-].C1=CC(=[N+](C)C)C=C2SC3=CC(N(C)C)=CC=C3N=C21 XQAXGZLFSSPBMK-UHFFFAOYSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 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
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 229940081735 acetylcellulose Drugs 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- JIMXXGFJRDUSRO-UHFFFAOYSA-N adamantane-1-carboxylic acid Chemical compound C1C(C2)CC3CC2CC1(C(=O)O)C3 JIMXXGFJRDUSRO-UHFFFAOYSA-N 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 1
- 125000006383 alkylpyridyl group Chemical group 0.000 description 1
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution 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
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229940116226 behenic acid Drugs 0.000 description 1
- HSVLGIFAXFDLMU-UHFFFAOYSA-M benzenesulfonate;1-methylpyridin-1-ium-4-carbaldehyde Chemical compound C[N+]1=CC=C(C=O)C=C1.[O-]S(=O)(=O)C1=CC=CC=C1 HSVLGIFAXFDLMU-UHFFFAOYSA-M 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- NHVFUGVOZKUGSO-IBGZPJMESA-N benzyl n-[(2s)-1-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound N([C@@H](C(C)C)C(=O)NC1=C2C(NC=3C=C(Cl)C=CC=3)=NC=NC2=NN1)C(=O)OCC1=CC=CC=C1 NHVFUGVOZKUGSO-IBGZPJMESA-N 0.000 description 1
- MSJHOJKVMMEMNX-UHFFFAOYSA-N benzylhydrazine;hydron;dichloride Chemical compound Cl.Cl.NNCC1=CC=CC=C1 MSJHOJKVMMEMNX-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011648 beta-carotene Substances 0.000 description 1
- 235000013734 beta-carotene Nutrition 0.000 description 1
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
- 229960002747 betacarotene Drugs 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- HNEGQIOMVPPMNR-IHWYPQMZSA-N citraconic acid Chemical compound OC(=O)C(/C)=C\C(O)=O HNEGQIOMVPPMNR-IHWYPQMZSA-N 0.000 description 1
- 238000005253 cladding Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229950006137 dexfosfoserine Drugs 0.000 description 1
- WOWBFOBYOAGEEA-UHFFFAOYSA-N diafenthiuron Chemical compound CC(C)C1=C(NC(=S)NC(C)(C)C)C(C(C)C)=CC(OC=2C=CC=CC=2)=C1 WOWBFOBYOAGEEA-UHFFFAOYSA-N 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- HJZSXJLBNQMPAG-UHFFFAOYSA-L dichloronickel diphenylphosphane propane Chemical compound CCC.Cl[Ni]Cl.P(c1ccccc1)c1ccccc1.P(c1ccccc1)c1ccccc1 HJZSXJLBNQMPAG-UHFFFAOYSA-L 0.000 description 1
- COLJYBDTTGVCKH-UHFFFAOYSA-L dichloronickel;diphenylphosphane;propane Chemical compound CCC.Cl[Ni]Cl.C=1C=CC=CC=1PC1=CC=CC=C1 COLJYBDTTGVCKH-UHFFFAOYSA-L 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- NQGIJDNPUZEBRU-UHFFFAOYSA-N dodecanoyl chloride Chemical compound CCCCCCCCCCCC(Cl)=O NQGIJDNPUZEBRU-UHFFFAOYSA-N 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- FPIQZBQZKBKLEI-UHFFFAOYSA-N ethyl 1-[[2-chloroethyl(nitroso)carbamoyl]amino]cyclohexane-1-carboxylate Chemical compound ClCCN(N=O)C(=O)NC1(C(=O)OCC)CCCCC1 FPIQZBQZKBKLEI-UHFFFAOYSA-N 0.000 description 1
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- SIVVHUQWDOGLJN-UHFFFAOYSA-N ethylsulfamic acid Chemical group CCNS(O)(=O)=O SIVVHUQWDOGLJN-UHFFFAOYSA-N 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- LTYRAPJYLUPLCI-UHFFFAOYSA-N glycolonitrile Chemical compound OCC#N LTYRAPJYLUPLCI-UHFFFAOYSA-N 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 239000003630 growth substance Substances 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- ANJPRQPHZGHVQB-UHFFFAOYSA-N hexyl isocyanate Chemical compound CCCCCCN=C=O ANJPRQPHZGHVQB-UHFFFAOYSA-N 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000003049 inorganic solvent Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- YDNLNVZZTACNJX-UHFFFAOYSA-N isocyanatomethylbenzene Chemical compound O=C=NCC1=CC=CC=C1 YDNLNVZZTACNJX-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 229960004488 linolenic acid Drugs 0.000 description 1
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 1
- 235000014666 liquid concentrate Nutrition 0.000 description 1
- 150000004668 long chain fatty acids Chemical class 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000012792 lyophilization process Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-N methyl sulfate Chemical compound COS(O)(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 description 1
- KVLPVPBJNOYAIH-UHFFFAOYSA-N n'-[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]-n,n-dimethylmethanimidamide Chemical compound C=12C(N=CN(C)C)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 KVLPVPBJNOYAIH-UHFFFAOYSA-N 0.000 description 1
- DFFHHZNPHSOWHE-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-3-morpholin-4-yl-1h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=C1C(N1CCOCC1)=NN2 DFFHHZNPHSOWHE-UHFFFAOYSA-N 0.000 description 1
- JETSWOCRRFLFKV-UHFFFAOYSA-N n-(3-chlorophenyl)-1h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C=3C=NNC=3N=CN=2)=C1 JETSWOCRRFLFKV-UHFFFAOYSA-N 0.000 description 1
- IXCVMLKVUBCMLW-UHFFFAOYSA-N n-(3-chlorophenyl)-3-(furan-2-ylmethylideneamino)-2h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C3=C(N=CC=4OC=CC=4)NN=C3N=CN=2)=C1 IXCVMLKVUBCMLW-UHFFFAOYSA-N 0.000 description 1
- SQHWYRXPBDFIDO-UHFFFAOYSA-N n-(3-chlorophenyl)-3-(pyridin-2-ylmethylideneamino)-2h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C3=C(N=CC=4N=CC=CC=4)NN=C3N=CN=2)=C1 SQHWYRXPBDFIDO-UHFFFAOYSA-N 0.000 description 1
- KWJZCWHUBVVUIP-UHFFFAOYSA-N n-(3-chlorophenyl)-3-[(4-pyridin-3-ylphenyl)methylideneamino]-2h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C3=C(N=CC=4C=CC(=CC=4)C=4C=NC=CC=4)NN=C3N=CN=2)=C1 KWJZCWHUBVVUIP-UHFFFAOYSA-N 0.000 description 1
- CDXLTEUKDHKTIC-UHFFFAOYSA-N n-(3-chlorophenyl)-3-[[2-(2-methyltetrazol-5-yl)phenyl]methylideneamino]-2h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound CN1N=NC(C=2C(=CC=CC=2)C=NC2=C3C(NC=4C=C(Cl)C=CC=4)=NC=NC3=NN2)=N1 CDXLTEUKDHKTIC-UHFFFAOYSA-N 0.000 description 1
- MPCNRHQKTUTHOO-UHFFFAOYSA-N n-(3-chlorophenyl)-3-[[2-(2h-tetrazol-5-yl)phenyl]methylideneamino]-2h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C3=C(N=CC=4C(=CC=CC=4)C4=NNN=N4)NN=C3N=CN=2)=C1 MPCNRHQKTUTHOO-UHFFFAOYSA-N 0.000 description 1
- IDDMSCZUUXWXFH-UHFFFAOYSA-N n-(3-chlorophenyl)-3-[[3-(2-methyltetrazol-5-yl)phenyl]methylideneamino]-2h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound CN1N=NC(C=2C=C(C=NC3=C4C(NC=5C=C(Cl)C=CC=5)=NC=NC4=NN3)C=CC=2)=N1 IDDMSCZUUXWXFH-UHFFFAOYSA-N 0.000 description 1
- VAQPCSCZTHXMJY-UHFFFAOYSA-N n-(3-chlorophenyl)-3-[[3-(2h-tetrazol-5-yl)phenyl]methylideneamino]-2h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C3=C(N=CC=4C=C(C=CC=4)C4=NNN=N4)NN=C3N=CN=2)=C1 VAQPCSCZTHXMJY-UHFFFAOYSA-N 0.000 description 1
- YHGHZZDRHADYGU-UHFFFAOYSA-N n-(3-chlorophenyl)-3-[[4-(1,3-thiazol-5-yl)phenyl]methylideneamino]-2h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound ClC1=CC=CC(NC=2C3=C(N=CC=4C=CC(=CC=4)C=4SC=NC=4)NN=C3N=CN=2)=C1 YHGHZZDRHADYGU-UHFFFAOYSA-N 0.000 description 1
- WNINNIZUSHQPHU-UHFFFAOYSA-N n-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]-3-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC=CC(C(=O)NCCNC=2C3=C(NC=4C=C(Cl)C=CC=4)N=CN=C3NN=2)=C1 WNINNIZUSHQPHU-UHFFFAOYSA-N 0.000 description 1
- DYTZTVZLRYMPRP-UHFFFAOYSA-N n-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]-4-nitrobenzamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)NCCNC1=NNC2=NC=NC(NC=3C=C(Cl)C=CC=3)=C12 DYTZTVZLRYMPRP-UHFFFAOYSA-N 0.000 description 1
- QULVPJAIIJJXMM-UHFFFAOYSA-N n-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]acetamide Chemical compound C=12C(NCCNC(=O)C)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 QULVPJAIIJJXMM-UHFFFAOYSA-N 0.000 description 1
- KTHPZMLWTMFKNQ-UHFFFAOYSA-N n-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]benzamide Chemical compound ClC1=CC=CC(NC=2C=3C(NCCNC(=O)C=4C=CC=CC=4)=NNC=3N=CN=2)=C1 KTHPZMLWTMFKNQ-UHFFFAOYSA-N 0.000 description 1
- BRUKMVGMORSWRI-UHFFFAOYSA-N n-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]formamide Chemical compound ClC1=CC=CC(NC=2C=3C(NCCNC=O)=NNC=3N=CN=2)=C1 BRUKMVGMORSWRI-UHFFFAOYSA-N 0.000 description 1
- MAXJMVODBXJSAY-UHFFFAOYSA-N n-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]furan-2-carboxamide Chemical compound ClC1=CC=CC(NC=2C=3C(NCCNC(=O)C=4OC=CC=4)=NNC=3N=CN=2)=C1 MAXJMVODBXJSAY-UHFFFAOYSA-N 0.000 description 1
- WHSPDOHUZPGCER-UHFFFAOYSA-N n-[2-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]ethyl]propanamide Chemical compound C=12C(NCCNC(=O)CC)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 WHSPDOHUZPGCER-UHFFFAOYSA-N 0.000 description 1
- GOQRJJJUKDOEDX-UHFFFAOYSA-N n-[3-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]propyl]-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NCCCNC1=NNC2=NC=NC(NC=3C=C(Cl)C=CC=3)=C12 GOQRJJJUKDOEDX-UHFFFAOYSA-N 0.000 description 1
- UADPPLWEOXEBHY-UHFFFAOYSA-N n-[3-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]propyl]acetamide Chemical compound C=12C(NCCCNC(=O)C)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 UADPPLWEOXEBHY-UHFFFAOYSA-N 0.000 description 1
- WJVLYEIKCQVFQZ-UHFFFAOYSA-N n-[3-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]propyl]benzamide Chemical compound ClC1=CC=CC(NC=2C=3C(NCCCNC(=O)C=4C=CC=CC=4)=NNC=3N=CN=2)=C1 WJVLYEIKCQVFQZ-UHFFFAOYSA-N 0.000 description 1
- ZVEZCNCIUJOJGE-UHFFFAOYSA-N n-[3-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]propyl]formamide Chemical compound ClC1=CC=CC(NC=2C=3C(NCCCNC=O)=NNC=3N=CN=2)=C1 ZVEZCNCIUJOJGE-UHFFFAOYSA-N 0.000 description 1
- YANJVJNPDUAITB-UHFFFAOYSA-N n-[3-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]propyl]methanesulfonamide Chemical compound C=12C(NCCCNS(=O)(=O)C)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 YANJVJNPDUAITB-UHFFFAOYSA-N 0.000 description 1
- NUEFKASECYQMSE-UHFFFAOYSA-N n-[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]-1,3-benzodioxole-4-carboxamide Chemical compound ClC1=CC=CC(NC=2C3=C(NC(=O)C=4C=5OCOC=5C=CC=4)NN=C3N=CN=2)=C1 NUEFKASECYQMSE-UHFFFAOYSA-N 0.000 description 1
- ZJXOLGYIMODJSC-UHFFFAOYSA-N n-[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]-1,3-benzodioxole-5-carboxamide Chemical compound ClC1=CC=CC(NC=2C3=C(NC(=O)C=4C=C5OCOC5=CC=4)NN=C3N=CN=2)=C1 ZJXOLGYIMODJSC-UHFFFAOYSA-N 0.000 description 1
- QCODHWORBJTAQE-UHFFFAOYSA-N n-[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]-2,2-dimethylpropanamide Chemical compound C12=C(NC(=O)C(C)(C)C)NN=C2N=CN=C1NC1=CC=CC(Cl)=C1 QCODHWORBJTAQE-UHFFFAOYSA-N 0.000 description 1
- TWIFGSGQIRLKHT-UHFFFAOYSA-N n-[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]benzamide Chemical compound ClC1=CC=CC(NC=2C3=C(NC(=O)C=4C=CC=CC=4)NN=C3N=CN=2)=C1 TWIFGSGQIRLKHT-UHFFFAOYSA-N 0.000 description 1
- HRYLVGIJHQKWJT-UHFFFAOYSA-N n-[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]furan-2-carboxamide Chemical compound ClC1=CC=CC(NC=2C3=C(NC(=O)C=4OC=CC=4)NN=C3N=CN=2)=C1 HRYLVGIJHQKWJT-UHFFFAOYSA-N 0.000 description 1
- NJZKFMLSHUSHCY-UHFFFAOYSA-N n-[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]hexanamide Chemical compound C12=C(NC(=O)CCCCC)NN=C2N=CN=C1NC1=CC=CC(Cl)=C1 NJZKFMLSHUSHCY-UHFFFAOYSA-N 0.000 description 1
- KOLHKNZGVZLNCS-UHFFFAOYSA-N n-[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]octanamide Chemical compound C12=C(NC(=O)CCCCCCC)NN=C2N=CN=C1NC1=CC=CC(Cl)=C1 KOLHKNZGVZLNCS-UHFFFAOYSA-N 0.000 description 1
- QHKATIIZRFLMPP-UHFFFAOYSA-N n-[4-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]butyl]acetamide Chemical compound C=12C(NCCCCNC(=O)C)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 QHKATIIZRFLMPP-UHFFFAOYSA-N 0.000 description 1
- MGXDCMFWJJFOJO-UHFFFAOYSA-N n-[4-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]butyl]benzamide Chemical compound ClC1=CC=CC(NC=2C=3C(NCCCCNC(=O)C=4C=CC=CC=4)=NNC=3N=CN=2)=C1 MGXDCMFWJJFOJO-UHFFFAOYSA-N 0.000 description 1
- AFTMPNXJJFAJQY-UHFFFAOYSA-N n-[4-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]butyl]formamide Chemical compound ClC1=CC=CC(NC=2C=3C(NCCCCNC=O)=NNC=3N=CN=2)=C1 AFTMPNXJJFAJQY-UHFFFAOYSA-N 0.000 description 1
- BJLGPLDKIWNZMI-UHFFFAOYSA-N n-[4-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]butyl]methanesulfonamide Chemical compound C=12C(NCCCCNS(=O)(=O)C)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 BJLGPLDKIWNZMI-UHFFFAOYSA-N 0.000 description 1
- SZEGUPRYCICECC-UHFFFAOYSA-N n-[[4-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]-4-hydroxybutanamide Chemical group C1=CC(CNC(=O)CCCO)=CC=C1NC1=C2C(NC=3C=C(Cl)C=CC=3)=NC=NC2=NN1 SZEGUPRYCICECC-UHFFFAOYSA-N 0.000 description 1
- HNHVTXYLRVGMHD-UHFFFAOYSA-N n-butyl isocyanate Chemical compound CCCCN=C=O HNHVTXYLRVGMHD-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- PSACHCMMPFMFAJ-UHFFFAOYSA-N nmm n-methylmorpholine Chemical compound CN1CCOCC1.CN1CCOCC1 PSACHCMMPFMFAJ-UHFFFAOYSA-N 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical class CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- REEZZSHJLXOIHL-UHFFFAOYSA-N octanoyl chloride Chemical compound CCCCCCCC(Cl)=O REEZZSHJLXOIHL-UHFFFAOYSA-N 0.000 description 1
- RAFYDKXYXRZODZ-UHFFFAOYSA-N octanoyl octanoate Chemical compound CCCCCCCC(=O)OC(=O)CCCCCCC RAFYDKXYXRZODZ-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical class C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 150000003009 phosphonic acids Chemical class 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- HLIBNTOXKQCYMV-UHFFFAOYSA-N propylsulfamic acid Chemical compound CCCNS(O)(=O)=O HLIBNTOXKQCYMV-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000003909 protein kinase inhibitor Substances 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 239000001944 prunus armeniaca kernel oil Substances 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 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
- 239000000376 reactant Substances 0.000 description 1
- 230000026267 regulation of growth Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003455 sulfinic acids Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- HNBSKZKKSRCJIQ-UHFFFAOYSA-N tert-butyl 4-[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NNC2=NC=NC(NC=3C=C(Cl)C=CC=3)=C12 HNBSKZKKSRCJIQ-UHFFFAOYSA-N 0.000 description 1
- WCWNLKCOEDKDAV-UHFFFAOYSA-N tert-butyl 4-[4-cyano-5-(dimethylaminomethylideneamino)-1h-pyrazol-3-yl]piperazine-1-carboxylate Chemical compound N#CC1=C(N=CN(C)C)NN=C1N1CCN(C(=O)OC(C)(C)C)CC1 WCWNLKCOEDKDAV-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
- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
- LSOZALWRNWQPLK-UHFFFAOYSA-N tert-butyl n-[(3-aminophenyl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=CC(N)=C1 LSOZALWRNWQPLK-UHFFFAOYSA-N 0.000 description 1
- UXWQXBSQQHAGMG-UHFFFAOYSA-N tert-butyl n-[(4-aminophenyl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=C(N)C=C1 UXWQXBSQQHAGMG-UHFFFAOYSA-N 0.000 description 1
- IATITYUCRWVUTN-UHFFFAOYSA-N tert-butyl n-[2-[3-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]propylamino]-2-oxoethyl]carbamate Chemical compound C=12C(NCCCNC(=O)CNC(=O)OC(C)(C)C)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 IATITYUCRWVUTN-UHFFFAOYSA-N 0.000 description 1
- ZKQFRQSIOZOHFN-UHFFFAOYSA-N tert-butyl n-[2-[4-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]butylamino]-2-oxoethyl]carbamate Chemical compound C=12C(NCCCCNC(=O)CNC(=O)OC(C)(C)C)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 ZKQFRQSIOZOHFN-UHFFFAOYSA-N 0.000 description 1
- ODBPMMIUAKHUPL-UHFFFAOYSA-N tert-butyl n-[2-[[4-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methylamino]-2-oxoethyl]carbamate Chemical compound C1=CC(CNC(=O)CNC(=O)OC(C)(C)C)=CC=C1NC1=C2C(NC=3C=C(Cl)C=CC=3)=NC=NC2=NN1 ODBPMMIUAKHUPL-UHFFFAOYSA-N 0.000 description 1
- BOSFFRLGNUWQRH-UHFFFAOYSA-N tert-butyl n-[2-[[4-cyano-5-(dimethylamino)-1-(methylideneamino)pyrazol-3-yl]amino]ethyl]carbamate Chemical compound CN(C)C1=C(C#N)C(NCCNC(=O)OC(C)(C)C)=NN1N=C BOSFFRLGNUWQRH-UHFFFAOYSA-N 0.000 description 1
- AIOUHZXVEYEYEF-UHFFFAOYSA-N tert-butyl n-[2-[[4-cyano-5-(dimethylaminomethylideneamino)-1h-pyrazol-3-yl]amino]ethyl]carbamate Chemical compound CN(C)C=NC=1NN=C(NCCNC(=O)OC(C)(C)C)C=1C#N AIOUHZXVEYEYEF-UHFFFAOYSA-N 0.000 description 1
- FCXFJTBDSHWNQI-UHFFFAOYSA-N tert-butyl n-[3-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]propyl]carbamate Chemical compound C=12C(NCCCNC(=O)OC(C)(C)C)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 FCXFJTBDSHWNQI-UHFFFAOYSA-N 0.000 description 1
- NNMGBPICEFOJCR-UHFFFAOYSA-N tert-butyl n-[4-[[4-(3-chloroanilino)-1h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]butyl]carbamate Chemical compound C=12C(NCCCCNC(=O)OC(C)(C)C)=NNC2=NC=NC=1NC1=CC=CC(Cl)=C1 NNMGBPICEFOJCR-UHFFFAOYSA-N 0.000 description 1
- DGPKWWQFXOBVQN-UHFFFAOYSA-N tert-butyl n-[[4-[[4-(3-chloroanilino)-2h-pyrazolo[3,4-d]pyrimidin-3-yl]amino]phenyl]methyl]carbamate Chemical compound C1=CC(CNC(=O)OC(C)(C)C)=CC=C1NC1=NNC2=NC=NC(NC=3C=C(Cl)C=CC=3)=C12 DGPKWWQFXOBVQN-UHFFFAOYSA-N 0.000 description 1
- SSVXDQDYFLJCCH-UHFFFAOYSA-N tert-butyl n-[[4-[[4-cyano-5-(dimethylamino)-1-(methylideneamino)pyrazol-3-yl]amino]phenyl]methyl]carbamate Chemical compound C=NN1C(N(C)C)=C(C#N)C(NC=2C=CC(CNC(=O)OC(C)(C)C)=CC=2)=N1 SSVXDQDYFLJCCH-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- BKBCDDYQJQGMNX-UHFFFAOYSA-N thiophene-2-carbonyl thiophene-2-carboxylate Chemical compound C=1C=CSC=1C(=O)OC(=O)C1=CC=CS1 BKBCDDYQJQGMNX-UHFFFAOYSA-N 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 150000004072 triols Chemical class 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Compounds Of Unknown Constitution (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH239996 | 1996-10-02 | ||
| CH239996 | 1996-10-02 | ||
| PCT/EP1997/005369 WO1998014450A1 (en) | 1996-10-02 | 1997-09-30 | Pyrimidine derivatives and processes for the preparation thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69732780D1 DE69732780D1 (de) | 2005-04-21 |
| DE69732780T2 true DE69732780T2 (de) | 2006-04-06 |
Family
ID=4232877
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69732780T Expired - Lifetime DE69732780T2 (de) | 1996-10-02 | 1997-09-30 | Pyrimiderivate und verfahren zu ihrer herstellung |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6251911B1 (https=) |
| EP (1) | EP0929553B1 (https=) |
| JP (1) | JP4205168B2 (https=) |
| AT (1) | ATE291022T1 (https=) |
| AU (1) | AU720135B2 (https=) |
| CA (1) | CA2266519C (https=) |
| DE (1) | DE69732780T2 (https=) |
| ES (1) | ES2239779T3 (https=) |
| WO (1) | WO1998014450A1 (https=) |
Families Citing this family (158)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2150113T3 (es) * | 1995-04-03 | 2000-11-16 | Novartis Ag | Derivados de pirazol y procedimientos para la preparacion de los mismos. |
| WO1998007726A1 (en) | 1996-08-23 | 1998-02-26 | Novartis Ag | Substituted pyrrolopyrimidines and processes for their preparation |
| AU755062B2 (en) | 1997-02-07 | 2002-12-05 | Princeton University | Engineered protein kinases which can utilize modified nucleotide triphosphate substrates |
| WO2000051998A1 (en) | 1999-03-02 | 2000-09-08 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compounds useful as reversible inhibitors of cathepsin s |
| US6440959B1 (en) * | 1999-04-21 | 2002-08-27 | Hoffman-La Roche Inc. | Pyrazolobenzodiazepines |
| US6610483B1 (en) * | 1999-07-23 | 2003-08-26 | Princeton University | Methods for identifying cellular responses attributable to signaling molecule inhibition and inhibitors thereof |
| US6420364B1 (en) | 1999-09-13 | 2002-07-16 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compound useful as reversible inhibitors of cysteine proteases |
| US7473691B2 (en) | 2000-09-15 | 2009-01-06 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| US6660731B2 (en) | 2000-09-15 | 2003-12-09 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| RU2340611C2 (ru) * | 2000-09-15 | 2008-12-10 | Вертекс Фармасьютикалз Инкорпорейтед | Производные пиразола, используемые в качестве ингибиторов протеинкиназы |
| US6613776B2 (en) | 2000-09-15 | 2003-09-02 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| SI1318997T1 (sl) * | 2000-09-15 | 2006-12-31 | Vertex Pharma | Pirazolne spojine, uporabne kot inhibitorji protein-kinaze |
| EP1317450B1 (en) | 2000-09-15 | 2006-11-22 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| NZ526472A (en) | 2000-12-21 | 2004-04-30 | Vertex Pharma | Pyrazole compounds useful as protein kinase inhibitors |
| US6593349B2 (en) * | 2001-03-19 | 2003-07-15 | Icagen, Inc. | Bisarylamines as potassium channel openers |
| US20050119251A1 (en) * | 2001-12-21 | 2005-06-02 | Jian-Min Fu | Nicotinamide derivatives and their use as therapeutic agents |
| MY141867A (en) | 2002-06-20 | 2010-07-16 | Vertex Pharma | Substituted pyrimidines useful as protein kinase inhibitors |
| US7585866B2 (en) * | 2002-07-31 | 2009-09-08 | Critical Outcome Technologies, Inc. | Protein tyrosine kinase inhibitors |
| DK1532145T3 (da) | 2002-08-02 | 2007-01-15 | Vertex Pharma | Pyrazolpræparater der er anvendelige som inhibitorer af GSK-3 |
| AU2003273675A1 (en) * | 2002-10-09 | 2004-05-04 | Wayne R. Danter | Protein tyrosine kinase inhibitors |
| EP1663204B1 (en) * | 2003-08-29 | 2014-05-07 | Exelixis, Inc. | C-kit modulators and methods of use |
| WO2005067546A2 (en) * | 2004-01-13 | 2005-07-28 | Ambit Biosciences Corporation | Pyrrolopyrimidine derivatives and analogs and their use in the treatment and prevention of diseases |
| AR051091A1 (es) | 2004-09-20 | 2006-12-20 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como inhibidores de la estearoil-coa desaturasa |
| EP1807085B1 (en) | 2004-09-20 | 2013-08-21 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
| EP2289510A1 (en) * | 2004-09-20 | 2011-03-02 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives for the treatment of diseases mediated by stearoyl-coa desaturase enzymes |
| CA2580762A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as therapeutic agents |
| CA2580857A1 (en) | 2004-09-20 | 2006-09-28 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
| AU2005286648A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-CoA desaturase inhibitors |
| JP5080256B2 (ja) * | 2004-09-20 | 2012-11-21 | ゼノン・ファーマシューティカルズ・インコーポレイテッド | 二環式複素環誘導体およびステアロイル−ＣｏＡデサチュラーゼ（ＳＣＤ）のインヒビターとしてのそれらの使用 |
| US7829712B2 (en) | 2004-09-20 | 2010-11-09 | Xenon Pharmaceuticals Inc. | Pyridazine derivatives for inhibiting human stearoyl-CoA-desaturase |
| AR052142A1 (es) * | 2004-11-18 | 2007-03-07 | Bristol Myers Squibb Co | Perla recubierta enterica que comprende ixabepilona, y preparacion y administracion de la misma |
| US9512125B2 (en) * | 2004-11-19 | 2016-12-06 | The Regents Of The University Of California | Substituted pyrazolo[3.4-D] pyrimidines as anti-inflammatory agents |
| EP1838712B8 (en) * | 2004-12-14 | 2011-10-12 | AstraZeneca AB | Pyrazolopyrimidine compounds as antitumor agents |
| AU2006343359A1 (en) * | 2005-06-03 | 2007-11-15 | Xenon Pharmaceuticals Inc. | Aminothiazole derivatives as human stearoyl-coa desaturase inhibitors |
| EP1954277B1 (en) | 2005-11-03 | 2017-01-18 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines useful as kinase inhibitors |
| BRPI0708615A2 (pt) * | 2006-03-07 | 2011-06-07 | Array Biopharma Inc | compostos de pirazol heterobicìclicos e métodos de uso |
| US20080161320A1 (en) * | 2006-09-11 | 2008-07-03 | Xiong Cai | Fused bicyclic pyrimidines as ptk inhibitors containing a zinc binding moiety |
| EP2061772A4 (en) * | 2006-09-11 | 2011-06-29 | Curis Inc | MULTIFUNCTIONAL SMALL MOLECULES AS PROLIFERATION-ACTIVE ACTIVE SUBSTANCES |
| US20100298557A1 (en) * | 2006-12-28 | 2010-11-25 | Taisho Pharmaceutical Co., Ltd | Pyrazolopyrimidine compound |
| JP5571387B2 (ja) | 2007-01-11 | 2014-08-13 | クリティカル・アウトカム・テクノロジーズ・インコーポレイテッド | 癌の治療のための化合物および方法 |
| EP1969935A1 (de) * | 2007-03-12 | 2008-09-17 | Bayer CropScience AG | 3,4-Disubstituierte Phenoxyphenylamidine und deren Verwendung als Fungizide |
| BRPI0808798A2 (pt) | 2007-03-12 | 2014-10-07 | Bayer Cropscience Ag | Fenoxifenilamidinas 3,5-dissubstituídas e seu uso como fungicidas |
| EP1969933A1 (de) * | 2007-03-12 | 2008-09-17 | Bayer CropScience AG | Dihalogenphenoxyphenylamidine und deren Verwendung als Fungizide |
| EP1969934A1 (de) * | 2007-03-12 | 2008-09-17 | Bayer CropScience AG | 4-Cycloalkyl-oder 4-arylsubstituierte Phenoxyphenylamidine und deren Verwendung als Fungizide |
| EP1969932A1 (de) * | 2007-03-12 | 2008-09-17 | Bayer CropScience AG | Phenoxyphenylamidine und deren Verwendung als Fungizide |
| BRPI0808786A2 (pt) * | 2007-03-12 | 2014-09-16 | Bayer Cropscience Ag | Di-halogenofenoxifenilamidinas e seu uso como fungicidas |
| JP2010520900A (ja) * | 2007-03-12 | 2010-06-17 | バイエル・クロツプサイエンス・アクチエンゲゼルシヤフト | フェノキシ置換されたフェニルアミジン誘導体及び殺真菌剤としてのその使用 |
| AU2008247592A1 (en) | 2007-05-02 | 2008-11-13 | Vertex Pharmaceuticals Incorporated | Thiazoles and pyrazoles useful as kinase inhibitors |
| CN101790532B (zh) | 2007-07-31 | 2013-11-20 | 沃泰克斯药物股份有限公司 | 5-氟-1H-吡唑并[3，4-b]吡啶-3-胺及其衍生物的制备方法 |
| GB2467670B (en) | 2007-10-04 | 2012-08-01 | Intellikine Inc | Chemical entities and therapeutic uses thereof |
| CA2710039C (en) * | 2007-12-26 | 2018-07-03 | Critical Outcome Technologies, Inc. | Semicarbazones, thiosemicarbazones and related compounds and methods for treatment of cancer |
| US8637542B2 (en) | 2008-03-14 | 2014-01-28 | Intellikine, Inc. | Kinase inhibitors and methods of use |
| JP5260114B2 (ja) * | 2008-03-31 | 2013-08-14 | 株式会社カネカ | Ｎ−アルコキシカルボニル−ｔｅｒｔ−ロイシンの製造法 |
| JP5788316B2 (ja) | 2008-07-08 | 2015-09-30 | インテリカイン， エルエルシー | キナーゼインヒビターおよび使用方法 |
| EP2318406B1 (en) * | 2008-07-17 | 2016-01-27 | Critical Outcome Technologies, Inc. | Thiosemicarbazone inhibitor compounds and cancer treatment methods |
| WO2010027921A1 (en) | 2008-09-03 | 2010-03-11 | Vertex Pharmaceuticals Incorporated | Co-crystals and pharmaceutical formulations comprising the same |
| US8476431B2 (en) | 2008-11-03 | 2013-07-02 | Itellikine LLC | Benzoxazole kinase inhibitors and methods of use |
| WO2010099139A2 (en) | 2009-02-25 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Combination anti-cancer therapy |
| US20110171124A1 (en) | 2009-02-26 | 2011-07-14 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the EMT status of tumor cells in vivo |
| WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| EP2401614A1 (en) | 2009-02-27 | 2012-01-04 | OSI Pharmaceuticals, LLC | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| JP2012519282A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
| EP2408479A1 (en) | 2009-03-18 | 2012-01-25 | OSI Pharmaceuticals, LLC | Combination cancer therapy comprising administration of an egfr inhibitor and an igf-1r inhibitor |
| WO2010122682A1 (ja) | 2009-04-24 | 2010-10-28 | 株式会社カネカ | Ｎ－アルコキシカルボニル－ｔｅｒｔ－ロイシンの製造法 |
| PE20121148A1 (es) | 2009-08-17 | 2012-09-07 | Intellikine Llc | Compuestos heterociclicos y usos de los mismos |
| US20120316187A1 (en) | 2009-11-13 | 2012-12-13 | Pangaea Biotech, S.L. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
| CA2999435A1 (en) | 2010-04-01 | 2011-10-06 | Critical Outcome Technologies Inc. | Compounds and method for treatment of hiv |
| EP2468883A1 (en) | 2010-12-22 | 2012-06-27 | Pangaea Biotech S.L. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
| US9134297B2 (en) | 2011-01-11 | 2015-09-15 | Icahn School Of Medicine At Mount Sinai | Method and compositions for treating cancer and related methods |
| EP2492688A1 (en) | 2011-02-23 | 2012-08-29 | Pangaea Biotech, S.A. | Molecular biomarkers for predicting response to antitumor treatment in lung cancer |
| US9295673B2 (en) | 2011-02-23 | 2016-03-29 | Intellikine Llc | Combination of mTOR inhibitors and P13-kinase inhibitors, and uses thereof |
| WO2012129145A1 (en) | 2011-03-18 | 2012-09-27 | OSI Pharmaceuticals, LLC | Nscle combination therapy |
| EP2702173A1 (en) | 2011-04-25 | 2014-03-05 | OSI Pharmaceuticals, LLC | Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment |
| SG2014011316A (en) | 2011-08-31 | 2014-06-27 | Genentech Inc | Diagnostic markers |
| US9056867B2 (en) | 2011-09-16 | 2015-06-16 | Novartis Ag | N-substituted heterocyclyl carboxamides |
| JP2014531213A (ja) | 2011-09-30 | 2014-11-27 | ジェネンテック， インコーポレイテッド | 上皮又は間葉の表現型の診断用メチル化マーカー、及び腫瘍又は腫瘍細胞におけるｅｇｆｒキナーゼ阻害薬に対する応答 |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| CN103483242A (zh) * | 2012-06-15 | 2014-01-01 | 上海朴颐化学科技有限公司 | 4-(2’-吡啶基)苄基肼及其中间体的制备方法 |
| WO2013190089A1 (en) | 2012-06-21 | 2013-12-27 | Pangaea Biotech, S.L. | Molecular biomarkers for predicting outcome in lung cancer |
| EP2976085A1 (en) | 2013-03-21 | 2016-01-27 | INSERM - Institut National de la Santé et de la Recherche Médicale | Method and pharmaceutical composition for use in the treatment of chronic liver diseases associated with a low hepcidin expression |
| WO2014153509A1 (en) | 2013-03-22 | 2014-09-25 | Millennium Pharmaceuticals, Inc. | Combination of catalytic mtorc 1/2 inhibitors and selective inhibitors of aurora a kinase |
| CN103709044A (zh) * | 2013-12-12 | 2014-04-09 | 江苏集贤绿色化学科技研究院有限公司 | 一种3-氯-4-氟苯胺盐酸盐的制备方法 |
| US20170027940A1 (en) | 2014-04-10 | 2017-02-02 | Stichting Het Nederlands Kanker Instituut | Method for treating cancer |
| TW201613919A (en) | 2014-07-02 | 2016-04-16 | Pharmacyclics Llc | Inhibitors of Bruton's tyrosine kinase |
| WO2016105503A1 (en) | 2014-12-24 | 2016-06-30 | Genentech, Inc. | Therapeutic, diagnostic and prognostic methods for cancer of the bladder |
| AU2016311426B2 (en) | 2015-08-26 | 2021-05-20 | Blueprint Medicines Corporation | Compounds and compositions useful for treating disorders related to NTRK |
| MX2018006195A (es) | 2015-11-19 | 2018-09-05 | Blueprint Medicines Corp | Compuestos y composiciones utiles para el tratamiento de trastornos relacionados con ntrk. |
| CN108101811A (zh) | 2016-11-25 | 2018-06-01 | 斯福瑞（南通）制药有限公司 | 生产n-叔丁氧羰基-2-氨基-3,3-二甲基丁酸的方法 |
| WO2018119183A2 (en) | 2016-12-22 | 2018-06-28 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| EA201992781A1 (ru) | 2017-05-22 | 2020-04-01 | Эмджен Инк. | Ингибиторы g12c kras и способы их применения |
| MA50077A (fr) | 2017-09-08 | 2020-07-15 | Amgen Inc | Inhibiteurs de kras g12c et leurs procédés d'utilisation |
| WO2019213516A1 (en) | 2018-05-04 | 2019-11-07 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| ES2995514T3 (en) | 2018-05-04 | 2025-02-10 | Amgen Inc | Kras g12c inhibitors and methods of using the same |
| EP3790886B1 (en) | 2018-05-10 | 2024-06-26 | Amgen Inc. | Kras g12c inhibitors for the treatment of cancer |
| CN113194752A (zh) | 2018-06-01 | 2021-07-30 | 康奈尔大学 | Pi3k相关疾病或病症的组合疗法 |
| ES2938987T3 (es) | 2018-06-01 | 2023-04-18 | Amgen Inc | Inhibidores de KRAS G12c y métodos de uso de los mismos |
| US20190375749A1 (en) | 2018-06-11 | 2019-12-12 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| ES3060664T3 (en) | 2018-06-12 | 2026-03-27 | Amgen Inc | Kras g12c inhibitors encompassing a piperazine ring and use thereof in the treatment of cancer |
| EP3860608A1 (en) | 2018-10-04 | 2021-08-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Egfr inhibitors for treating keratodermas |
| JP7516029B2 (ja) | 2018-11-16 | 2024-07-16 | アムジエン・インコーポレーテツド | Ｋｒａｓ ｇ１２ｃ阻害剤化合物の重要な中間体の改良合成法 |
| US11053226B2 (en) | 2018-11-19 | 2021-07-06 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
| JP7377679B2 (ja) | 2018-11-19 | 2023-11-10 | アムジエン・インコーポレーテツド | がん治療のためのｋｒａｓｇ１２ｃ阻害剤及び１種以上の薬学的に活性な追加の薬剤を含む併用療法 |
| TWI844602B (zh) | 2018-12-20 | 2024-06-11 | 美商安進公司 | Kif18a抑制劑 |
| EP3898616B1 (en) | 2018-12-20 | 2024-10-02 | Amgen Inc. | Heteroaryl amides useful as kif18a inhibitors |
| JP7676308B2 (ja) | 2018-12-20 | 2025-05-14 | アムジエン・インコーポレーテツド | Ｋｉｆ１８ａ阻害剤として有用なヘテロアリールアミド |
| WO2020132651A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Kif18a inhibitors |
| WO2020180768A1 (en) | 2019-03-01 | 2020-09-10 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
| CN113727758A (zh) | 2019-03-01 | 2021-11-30 | 锐新医药公司 | 双环杂环基化合物及其用途 |
| EP3738593A1 (en) | 2019-05-14 | 2020-11-18 | Amgen, Inc | Dosing of kras inhibitor for treatment of cancers |
| NZ782284A (en) | 2019-05-21 | 2024-11-29 | Amgen Inc | Solid state forms |
| EP4007756B1 (en) | 2019-08-02 | 2025-12-24 | Amgen Inc. | Kif18a inhibitors |
| AU2020326627B2 (en) | 2019-08-02 | 2026-01-29 | Amgen Inc. | KIF18A inhibitors |
| WO2021026099A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
| US12540129B2 (en) | 2019-08-02 | 2026-02-03 | Amgen Inc. | KIF18A inhibitors |
| EP4684786A3 (en) | 2019-10-24 | 2026-04-08 | Amgen Inc. | Pyridopyrimidine derivatives useful as kras g12c and kras g12d inhibitors in the treatment of cancer |
| CN120699039A (zh) | 2019-11-04 | 2025-09-26 | 锐新医药公司 | Ras抑制剂 |
| WO2021091956A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
| MX2022005359A (es) | 2019-11-04 | 2022-06-02 | Revolution Medicines Inc | Inhibidores de ras. |
| TW202128688A (zh) | 2019-11-08 | 2021-08-01 | 美商銳新醫藥公司 | 雙環雜芳基化合物及其用途 |
| WO2021097207A1 (en) | 2019-11-14 | 2021-05-20 | Amgen Inc. | Improved synthesis of kras g12c inhibitor compound |
| JP2023501528A (ja) | 2019-11-14 | 2023-01-18 | アムジエン・インコーポレーテツド | Ｋｒａｓ ｇ１２ｃ阻害剤化合物の改善された合成 |
| EP4065231A1 (en) | 2019-11-27 | 2022-10-05 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| CN114929279A (zh) | 2020-01-07 | 2022-08-19 | 锐新医药公司 | Shp2抑制剂给药和治疗癌症的方法 |
| IL299131A (en) | 2020-06-18 | 2023-02-01 | Revolution Medicines Inc | Methods for delaying, preventing and treating acquired resistance to RAS inhibitors |
| MX2023002248A (es) | 2020-09-03 | 2023-05-16 | Revolution Medicines Inc | Uso de inhibidores de sos1 para tratar neoplasias malignas con mutaciones de shp2. |
| MX2023003060A (es) | 2020-09-15 | 2023-04-05 | Revolution Medicines Inc | Derivados indolicos como inhibidores de ras en el tratamiento del cancer. |
| US20240051956A1 (en) | 2020-12-22 | 2024-02-15 | Qilu Regor Therapeutics Inc. | Sos1 inhibitors and uses thereof |
| WO2022235866A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| AU2022268962A1 (en) | 2021-05-05 | 2023-12-14 | Revolution Medicines, Inc. | Ras inhibitors for the treatment of cancer |
| CA3217393A1 (en) | 2021-05-05 | 2022-11-10 | Elena S. Koltun | Ras inhibitors |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| TW202340214A (zh) | 2021-12-17 | 2023-10-16 | 美商健臻公司 | 做為shp2抑制劑之吡唑并吡𠯤化合物 |
| EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
| WO2023172858A1 (en) | 2022-03-07 | 2023-09-14 | Amgen Inc. | A process for preparing 4-methyl-2-propan-2-yl-pyridine-3-carbonitrile |
| CN119136806A (zh) | 2022-03-08 | 2024-12-13 | 锐新医药公司 | 用于治疗免疫难治性肺癌的方法 |
| TW202345806A (zh) | 2022-03-31 | 2023-12-01 | 美商艾伯維有限公司 | 噻唑并〔５，４－ｂ〕吡啶ｍａｌｔ－１抑制劑 |
| WO2023240263A1 (en) | 2022-06-10 | 2023-12-14 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| AU2023358792A1 (en) | 2022-10-14 | 2025-04-17 | Black Diamond Therapeutics, Inc. | Methods of treating cancers using isoquinoline or 6-aza-quinoline derivatives |
| EP4687905A1 (en) | 2023-03-30 | 2026-02-11 | Revolution Medicines, Inc. | Compositions for inducing ras gtp hydrolysis and uses thereof |
| CN121263418A (zh) | 2023-04-07 | 2026-01-02 | 锐新医药公司 | 大环ras抑制剂 |
| KR20260005904A (ko) | 2023-04-07 | 2026-01-12 | 레볼루션 메디슨즈, 인크. | 매크로사이클릭 ras 억제제 |
| KR20250172857A (ko) | 2023-04-14 | 2025-12-09 | 레볼루션 메디슨즈, 인크. | Ras 억제제의 결정형 |
| AU2024252105A1 (en) | 2023-04-14 | 2025-10-16 | Revolution Medicines, Inc. | Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof |
| AU2024265078A1 (en) | 2023-05-04 | 2025-12-11 | Revolution Medicines, Inc. | Combination therapy for a ras related disease or disorder |
| IL326136A (en) | 2023-08-07 | 2026-03-01 | Revolution Medicines Inc | RMC-6291 for use in the treatment of a disease or disorder associated with the RAS protein |
| US20250154171A1 (en) | 2023-10-12 | 2025-05-15 | Revolution Medicines, Inc. | Ras inhibitors |
| TW202542151A (zh) | 2023-12-22 | 2025-11-01 | 美商銳格醫藥有限公司 | Ｓｏｓ１抑制劑及其用途 |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
| US20250375445A1 (en) | 2024-06-07 | 2025-12-11 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| WO2025265060A1 (en) | 2024-06-21 | 2025-12-26 | Revolution Medicines, Inc. | Therapeutic compositions and methods for managing treatment-related effects |
| WO2026006747A1 (en) | 2024-06-28 | 2026-01-02 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026015801A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015790A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015796A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015825A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Use of ras inhibitor for treating pancreatic cancer |
| WO2026050446A1 (en) | 2024-08-29 | 2026-03-05 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026072904A2 (en) | 2024-09-26 | 2026-04-02 | Revolution Medicines, Inc. | Compositions and methods for treating lung cancer |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3036390A1 (de) | 1980-09-26 | 1982-05-13 | Troponwerke GmbH & Co KG, 5000 Köln | Neue pyrrolo-pyrimidine, verfahren zu ihrer herstellung und ihre verwendung bei der herstellung von biologischen wirkstoffen |
| US5409930A (en) | 1991-05-10 | 1995-04-25 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| IL112248A0 (en) | 1994-01-25 | 1995-03-30 | Warner Lambert Co | Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them |
| IL112249A (en) | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
| EP0682027B1 (de) | 1994-05-03 | 1997-10-15 | Novartis AG | Pyrrolopyrimidinderivate mit antiproliferativer Wirkung |
| JP4145955B2 (ja) | 1994-09-29 | 2008-09-03 | ノバルティス アクチェンゲゼルシャフト | ピロロ〔２，３−ｄ〕ピリミジン及びその使用 |
| ES2150113T3 (es) | 1995-04-03 | 2000-11-16 | Novartis Ag | Derivados de pirazol y procedimientos para la preparacion de los mismos. |
| US6403599B1 (en) | 1995-11-08 | 2002-06-11 | Pfizer Inc | Corticotropin releasing factor antagonists |
| ATE247469T1 (de) | 1995-06-07 | 2003-09-15 | Pfizer | Heterocyclische kondensierte pyrimidin-derivate |
| MX9800215A (es) | 1995-07-06 | 1998-03-31 | Novartis Ag | Pirrolopirimidas y procesos para su preparacion. |
| ATE217873T1 (de) | 1996-01-23 | 2002-06-15 | Novartis Erfind Verwalt Gmbh | Pyrrolopyrimidinen und verfahren zu deren herstellung |
| GB9604361D0 (en) | 1996-02-29 | 1996-05-01 | Pharmacia Spa | 4-Substituted pyrrolopyrimidine compounds as tyrosine kinase inhibitors |
| ES2203793T3 (es) | 1996-03-15 | 2004-04-16 | Novartis Ag | N-7-heterociclil-pirrolo(2,3-d)pirimidinas y su empleo. |
| WO1998007726A1 (en) | 1996-08-23 | 1998-02-26 | Novartis Ag | Substituted pyrrolopyrimidines and processes for their preparation |
| AU4779897A (en) | 1996-10-02 | 1998-04-24 | Novartis Ag | Fused pyrazole derivatives and processes for their preparation |
-
1997
- 1997-09-30 US US09/269,823 patent/US6251911B1/en not_active Expired - Fee Related
- 1997-09-30 ES ES97911163T patent/ES2239779T3/es not_active Expired - Lifetime
- 1997-09-30 AU AU48642/97A patent/AU720135B2/en not_active Ceased
- 1997-09-30 DE DE69732780T patent/DE69732780T2/de not_active Expired - Lifetime
- 1997-09-30 WO PCT/EP1997/005369 patent/WO1998014450A1/en not_active Ceased
- 1997-09-30 EP EP97911163A patent/EP0929553B1/en not_active Expired - Lifetime
- 1997-09-30 JP JP51623198A patent/JP4205168B2/ja not_active Expired - Fee Related
- 1997-09-30 AT AT97911163T patent/ATE291022T1/de not_active IP Right Cessation
- 1997-09-30 CA CA002266519A patent/CA2266519C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP4205168B2 (ja) | 2009-01-07 |
| AU4864297A (en) | 1998-04-24 |
| WO1998014450A1 (en) | 1998-04-09 |
| ATE291022T1 (de) | 2005-04-15 |
| EP0929553B1 (en) | 2005-03-16 |
| CA2266519C (en) | 2007-01-23 |
| DE69732780D1 (de) | 2005-04-21 |
| CA2266519A1 (en) | 1998-04-09 |
| JP2001501216A (ja) | 2001-01-30 |
| EP0929553A1 (en) | 1999-07-21 |
| AU720135B2 (en) | 2000-05-25 |
| US6251911B1 (en) | 2001-06-26 |
| ES2239779T3 (es) | 2005-10-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69732780T2 (de) | Pyrimiderivate und verfahren zu ihrer herstellung | |
| DE69738468T2 (de) | Substituierte pyrrolopyrimidine und verfahren zu ihrer herstellung | |
| DE69619114T2 (de) | Pyrolopyrimidine und verfahren zu ihrer herstellung | |
| DE69609602T2 (de) | Pyrazolderivate und verfahren zu deren herstellung | |
| DE69712745T2 (de) | Pyrrolopyrimidinen und verfahren zu deren herstellung | |
| EP1339716B1 (de) | lactam-substituierte pyrazolopyridinderivate | |
| EP0682027B1 (de) | Pyrrolopyrimidinderivate mit antiproliferativer Wirkung | |
| DE60101479T2 (de) | Betacarbolinderivate als phosphodiesterase-inhibitoren | |
| DE69909818T2 (de) | Pyrazolopyimidinon-derivate zur behandlung von impotenz | |
| DE60319255T2 (de) | Pyrimidoverbindungen mit antiproliferativer wirkung | |
| DE60117607T2 (de) | Verfahren zur Behandlung von mit p38-Kinase assoziierten Leiden und Pyrrolotriazin-Verbindungen als Kinaseinhibitoren. | |
| DE60315615T2 (de) | Tricyclische verbindungen basierend auf thiophen und arzneimittel, die diese umfassen | |
| DE60203995T2 (de) | Triazoloverbindungen als mmp-inhibitoren | |
| DE60030002T2 (de) | Für den adenosin-a1-a2a-und-a3-rezeptor spezifische verbindungen und verwendungen davon | |
| DE602005004287T2 (de) | Pyrrazolopyrimidinderivate | |
| DE69716810T2 (de) | 2,3-Disubstituierte-(5,6)-heteroarylkondensierte-pyrimidin-4-one | |
| DE60209721T2 (de) | Oxazolo- und furopyrimidine und deren verwendung als medikamente gegen tumore | |
| DE10057751A1 (de) | Neue Carbamat-substituierte Pyrazolopyridinderivate | |
| DE112013002484T5 (de) | Pteridinketon-Derivat und Anwendungen desselben als EGFR-, BLK- und FLT3-Inhibitor | |
| DE69916627T2 (de) | 5-heterozyklyl-pyrazolo[4,3-d]pyrimidin-7-one für die behandlung von männlichen erectilen dysfunktionen | |
| DE60305058T2 (de) | Imidazoquinoline derivate als adenosine a3 rezeptor liganden | |
| DE3722992A1 (de) | Neue imidazo-pyridine und purine, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung | |
| DE69824195T2 (de) | Dipyridoimidazolderivate zur behandlung von störungen des zentralen nervensystems | |
| EP0575425B1 (de) | VERWENDUNG VON OXAZOLO- 2,3-a]ISOINDOL- UND IMIDAZO 2,1-a]ISOINDOL-DERIVATEN ALS ANTIVIRALE ARZNEIMITTEL SOWIE NEUE OXAZOLO 2,3-a]ISOINDOL-DERIVATEN | |
| DE602004012552T2 (de) | Diaminopyrrolochinazoline als protein-tyrosin-phosphatase-inhibitoren |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8328 | Change in the person/name/address of the agent |
Representative=s name: KROHER, STROBEL RECHTS- UND PATENTANWAELTE, 80336 |
|
| 8328 | Change in the person/name/address of the agent |
Representative=s name: DR. SCHOEN & PARTNER, 80336 MUENCHEN |