CN102746298A - PI3Kα的吡啶并嘧啶酮抑制剂 - Google Patents
PI3Kα的吡啶并嘧啶酮抑制剂 Download PDFInfo
- Publication number
- CN102746298A CN102746298A CN2012102106887A CN201210210688A CN102746298A CN 102746298 A CN102746298 A CN 102746298A CN 2012102106887 A CN2012102106887 A CN 2012102106887A CN 201210210688 A CN201210210688 A CN 201210210688A CN 102746298 A CN102746298 A CN 102746298A
- Authority
- CN
- China
- Prior art keywords
- ketone
- pyrimidines
- methyl
- optional substituted
- base
- 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.)
- Pending
Links
- 239000003112 inhibitor Substances 0.000 title description 6
- IAAQUOVTPAMQCR-UHFFFAOYSA-N 1h-pyrido[3,2-d]pyrimidin-2-one Chemical compound C1=CC=C2NC(=O)N=CC2=N1 IAAQUOVTPAMQCR-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 245
- 238000000034 method Methods 0.000 claims abstract description 77
- 150000003839 salts Chemical class 0.000 claims abstract description 37
- 239000012453 solvate Substances 0.000 claims abstract description 18
- -1 pyrazole-3-yl Chemical group 0.000 claims description 106
- 125000000217 alkyl group Chemical group 0.000 claims description 74
- 125000003545 alkoxy group Chemical group 0.000 claims description 62
- 125000001072 heteroaryl group Chemical group 0.000 claims description 61
- 239000001257 hydrogen Substances 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- 206010028980 Neoplasm Diseases 0.000 claims description 58
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 53
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 51
- XLJMAIOERFSOGZ-UHFFFAOYSA-N cyanic acid Chemical compound OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 claims description 46
- 125000005843 halogen group Chemical group 0.000 claims description 46
- 201000011510 cancer Diseases 0.000 claims description 44
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 41
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 38
- 201000010099 disease Diseases 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 33
- 150000002431 hydrogen Chemical class 0.000 claims description 32
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 31
- 125000003107 substituted aryl group Chemical group 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 24
- 125000003282 alkyl amino group Chemical group 0.000 claims description 23
- 125000001188 haloalkyl group Chemical group 0.000 claims description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000003368 amide group Chemical group 0.000 claims description 21
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 125000002252 acyl group Chemical group 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 239000003981 vehicle Substances 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 10
- 206010006187 Breast cancer Diseases 0.000 claims description 9
- 208000026310 Breast neoplasm Diseases 0.000 claims description 9
- 208000005017 glioblastoma Diseases 0.000 claims description 9
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 9
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 9
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 8
- 206010009944 Colon cancer Diseases 0.000 claims description 8
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 8
- 206010033128 Ovarian cancer Diseases 0.000 claims description 8
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 8
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- 201000010881 cervical cancer Diseases 0.000 claims description 8
- 201000010989 colorectal carcinoma Diseases 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- 201000001441 melanoma Diseases 0.000 claims description 8
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 7
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 7
- 206010038038 rectal cancer Diseases 0.000 claims description 7
- 201000001275 rectum cancer Diseases 0.000 claims description 7
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 6
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 201000003914 endometrial carcinoma Diseases 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 6
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 6
- 150000003222 pyridines Chemical class 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 5
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 5
- 208000033781 Thyroid carcinoma Diseases 0.000 claims description 5
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 201000000498 stomach carcinoma Diseases 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 201000002510 thyroid cancer Diseases 0.000 claims description 5
- 208000013077 thyroid gland carcinoma Diseases 0.000 claims description 5
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 5
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 4
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 4
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 4
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 4
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 claims description 4
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 4
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 3
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 2
- CHZVGYLVZMHCSX-UHFFFAOYSA-N 5-(2-amino-8-ethyl-4-methyl-7-oxopyrido[2,3-d]pyrimidin-6-yl)thiophene-2-carbonitrile Chemical compound O=C1N(CC)C2=NC(N)=NC(C)=C2C=C1C1=CC=C(C#N)S1 CHZVGYLVZMHCSX-UHFFFAOYSA-N 0.000 claims 1
- 239000002585 base Substances 0.000 description 252
- 238000005160 1H NMR spectroscopy Methods 0.000 description 93
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 91
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 78
- 108091007960 PI3Ks Proteins 0.000 description 68
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 68
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 68
- 238000006243 chemical reaction Methods 0.000 description 68
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 56
- 239000000243 solution Substances 0.000 description 55
- 239000002904 solvent Substances 0.000 description 49
- 239000000203 mixture Substances 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
- 239000003795 chemical substances by application Substances 0.000 description 44
- 210000004027 cell Anatomy 0.000 description 41
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 40
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- 239000003153 chemical reaction reagent Substances 0.000 description 34
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- 239000007787 solid Substances 0.000 description 33
- 238000002360 preparation method Methods 0.000 description 31
- 238000003756 stirring Methods 0.000 description 30
- 229910052799 carbon Inorganic materials 0.000 description 28
- 239000011734 sodium Substances 0.000 description 24
- 108091000080 Phosphotransferase Proteins 0.000 description 23
- 102000020233 phosphotransferase Human genes 0.000 description 23
- 239000000047 product Substances 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 23
- 125000004429 atom Chemical group 0.000 description 22
- 230000000694 effects Effects 0.000 description 22
- 238000010438 heat treatment Methods 0.000 description 22
- 229910052760 oxygen Inorganic materials 0.000 description 21
- 108090000623 proteins and genes Proteins 0.000 description 21
- 102000004169 proteins and genes Human genes 0.000 description 20
- 230000027455 binding Effects 0.000 description 19
- 239000000460 chlorine Substances 0.000 description 19
- 239000001301 oxygen Substances 0.000 description 19
- 235000018102 proteins Nutrition 0.000 description 19
- 229920006395 saturated elastomer Polymers 0.000 description 19
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 18
- 238000005481 NMR spectroscopy Methods 0.000 description 18
- 125000004122 cyclic group Chemical group 0.000 description 18
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 18
- 238000001035 drying Methods 0.000 description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 17
- 239000000376 reactant Substances 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 150000001721 carbon Chemical group 0.000 description 16
- 238000001704 evaporation Methods 0.000 description 16
- 125000002769 thiazolinyl group Chemical group 0.000 description 16
- 239000012267 brine Substances 0.000 description 15
- 239000003814 drug Substances 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- 239000002512 suppressor factor Substances 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- 239000000651 prodrug Substances 0.000 description 14
- 229940002612 prodrug Drugs 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- 238000005406 washing Methods 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- 229910052801 chlorine Inorganic materials 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 11
- 230000003203 everyday effect Effects 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 10
- 150000001336 alkenes Chemical class 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 230000026731 phosphorylation Effects 0.000 description 10
- 238000006366 phosphorylation reaction Methods 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 230000001105 regulatory effect Effects 0.000 description 10
- 238000012216 screening Methods 0.000 description 10
- 230000004083 survival effect Effects 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- 102000001253 Protein Kinase Human genes 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
- 230000037396 body weight Effects 0.000 description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
- 210000004907 gland Anatomy 0.000 description 9
- 108060006633 protein kinase Proteins 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 206010039491 Sarcoma Diseases 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000003513 alkali Substances 0.000 description 8
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 230000008021 deposition Effects 0.000 description 8
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 8
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 239000002994 raw material Substances 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 7
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 7
- 230000006837 decompression Effects 0.000 description 7
- 238000010790 dilution Methods 0.000 description 7
- 239000012895 dilution Substances 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 7
- 101100297694 Arabidopsis thaliana PIP2-7 gene Proteins 0.000 description 6
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- 101100456541 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) MEC3 gene Proteins 0.000 description 6
- 101100483663 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) UFD1 gene Proteins 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 6
- 125000004472 dialkylaminosulfonyl group Chemical group 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- 238000003810 ethyl acetate extraction Methods 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000011630 iodine Substances 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 108020001756 ligand binding domains Proteins 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 238000011580 nude mouse model Methods 0.000 description 6
- IISCAMGOVRGLRZ-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine-6-carbonitrile Chemical compound N1=CN=CC2=CC(C#N)=CN=C21 IISCAMGOVRGLRZ-UHFFFAOYSA-N 0.000 description 6
- 206010041823 squamous cell carcinoma Diseases 0.000 description 6
- 208000011580 syndromic disease Diseases 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- 238000010792 warming Methods 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
- 241000228143 Penicillium Species 0.000 description 5
- 108091008611 Protein Kinase B Proteins 0.000 description 5
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 5
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 5
- 229910004298 SiO 2 Inorganic materials 0.000 description 5
- 125000004442 acylamino group Chemical group 0.000 description 5
- 125000004423 acyloxy group Chemical group 0.000 description 5
- 150000001408 amides Chemical group 0.000 description 5
- 125000002431 aminoalkoxy group Chemical group 0.000 description 5
- 239000003855 balanced salt solution Substances 0.000 description 5
- 244000309466 calf Species 0.000 description 5
- 229910002091 carbon monoxide Inorganic materials 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 238000007865 diluting Methods 0.000 description 5
- 238000006073 displacement reaction Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003797 essential amino acid Substances 0.000 description 5
- 235000020776 essential amino acid Nutrition 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 239000002207 metabolite Substances 0.000 description 5
- 238000012544 monitoring process Methods 0.000 description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 description 5
- XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 5
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000012266 salt solution Substances 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 150000003457 sulfones Chemical class 0.000 description 5
- 239000000829 suppository Substances 0.000 description 5
- 230000004614 tumor growth Effects 0.000 description 5
- 238000001291 vacuum drying Methods 0.000 description 5
- 238000003828 vacuum filtration Methods 0.000 description 5
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- 206010024612 Lipoma Diseases 0.000 description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 125000005090 alkenylcarbonyl group Chemical group 0.000 description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 4
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 4
- 125000004414 alkyl thio group Chemical group 0.000 description 4
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 4
- 230000000975 bioactive effect Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000004327 boric acid Substances 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000005094 computer simulation Methods 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 206010016629 fibroma Diseases 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 201000011066 hemangioma Diseases 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- AMWRITDGCCNYAT-UHFFFAOYSA-L hydroxy(oxo)manganese;manganese Chemical compound [Mn].O[Mn]=O.O[Mn]=O AMWRITDGCCNYAT-UHFFFAOYSA-L 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 230000002969 morbid Effects 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 150000003141 primary amines Chemical class 0.000 description 4
- UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical compound N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 description 4
- FREJAOSUHFGDBW-UHFFFAOYSA-N pyrimidine-5-carbaldehyde Chemical compound O=CC1=CN=CN=C1 FREJAOSUHFGDBW-UHFFFAOYSA-N 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 206010001233 Adenoma benign Diseases 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 201000008808 Fibrosarcoma Diseases 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 208000032612 Glial tumor Diseases 0.000 description 3
- 206010018338 Glioma Diseases 0.000 description 3
- 101000605639 Homo sapiens Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Proteins 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 102100038332 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Human genes 0.000 description 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- 206010043276 Teratoma Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 208000009956 adenocarcinoma Diseases 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 3
- 230000036983 biotransformation Effects 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000004590 computer program Methods 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 229940000406 drug candidate Drugs 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- 230000006303 immediate early viral mRNA transcription Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 2
- NPTGVVKPLWFPPX-UHFFFAOYSA-N 2-amino-4-chloro-6-methylpyrimidine Chemical compound CC1=CC(Cl)=NC(N)=N1 NPTGVVKPLWFPPX-UHFFFAOYSA-N 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
- ZHRDGKZWGPJCSJ-UHFFFAOYSA-N 4-n-cyclohexyl-2-n-ethyl-5-iodo-6-methylpyrimidine-2,4-diamine Chemical compound CCNC1=NC(C)=C(I)C(NC2CCCCC2)=N1 ZHRDGKZWGPJCSJ-UHFFFAOYSA-N 0.000 description 2
- MAPPVNNJRAFIGP-UHFFFAOYSA-N 4-n-cyclohexyl-2-n-ethyl-6-methylpyrimidine-2,4-diamine Chemical compound CCNC1=NC(C)=CC(NC2CCCCC2)=N1 MAPPVNNJRAFIGP-UHFFFAOYSA-N 0.000 description 2
- PPFIFJQSPMSQKZ-UHFFFAOYSA-N 4-n-ethylpyrimidine-2,4-diamine Chemical compound CCNC1=CC=NC(N)=N1 PPFIFJQSPMSQKZ-UHFFFAOYSA-N 0.000 description 2
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 2
- 108010013043 Acetylesterase Proteins 0.000 description 2
- 208000003200 Adenoma Diseases 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 201000003076 Angiosarcoma Diseases 0.000 description 2
- 0 CCN(C(C(C=C1C2=N*(C)(*)NN2)=C(C)N=C(N)N)=C)C1=O Chemical compound CCN(C(C(C=C1C2=N*(C)(*)NN2)=C(C)N=C(N)N)=C)C1=O 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 206010007275 Carcinoid tumour Diseases 0.000 description 2
- 201000005262 Chondroma Diseases 0.000 description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- 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 2
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- KGWDUNBJIMUFAP-KVVVOXFISA-N Ethanolamine Oleate Chemical compound NCCO.CCCCCCCC\C=C/CCCCCCCC(O)=O KGWDUNBJIMUFAP-KVVVOXFISA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 208000007569 Giant Cell Tumors Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 208000001258 Hemangiosarcoma Diseases 0.000 description 2
- 101000779418 Homo sapiens RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 208000018142 Leiomyosarcoma Diseases 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 2
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 2
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 208000008383 Wilms tumor Diseases 0.000 description 2
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 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 2
- MOQOOKGPCBQMCY-UHFFFAOYSA-N acetic acid;hexane Chemical compound CC(O)=O.CCCCCC MOQOOKGPCBQMCY-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 2
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 2
- 125000005195 alkyl amino carbonyloxy group Chemical group 0.000 description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- CUBCNYWQJHBXIY-UHFFFAOYSA-N benzoic acid;2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1O CUBCNYWQJHBXIY-UHFFFAOYSA-N 0.000 description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 150000001722 carbon compounds Chemical class 0.000 description 2
- 208000002458 carcinoid tumor Diseases 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 208000002445 cystadenocarcinoma Diseases 0.000 description 2
- 238000013016 damping Methods 0.000 description 2
- 230000030609 dephosphorylation Effects 0.000 description 2
- 238000006209 dephosphorylation reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 125000005202 dialkylaminocarbonyloxy group Chemical group 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 229960005156 digoxin Drugs 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000005113 hydroxyalkoxy group Chemical group 0.000 description 2
- 230000003463 hyperproliferative effect Effects 0.000 description 2
- 150000002466 imines Chemical group 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 125000005956 isoquinolyl group Chemical group 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 206010027191 meningioma Diseases 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical compound OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 238000006053 organic reaction Methods 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- IDXKTTNFXPPXJY-UHFFFAOYSA-N pyrimidin-1-ium;chloride Chemical compound Cl.C1=CN=CN=C1 IDXKTTNFXPPXJY-UHFFFAOYSA-N 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000011435 rock Substances 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000007614 solvation Methods 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
- OHOVBSAWJQSRDD-UHFFFAOYSA-N thiophen-2-yloxyboronic acid Chemical compound OB(O)OC1=CC=CS1 OHOVBSAWJQSRDD-UHFFFAOYSA-N 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-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
- 230000009466 transformation Effects 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- NQBWNECTZUOWID-UHFFFAOYSA-N (E)-cinnamyl (E)-cinnamate Natural products C=1C=CC=CC=1C=CC(=O)OCC=CC1=CC=CC=C1 NQBWNECTZUOWID-UHFFFAOYSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- ANQSYQOHGAJRKN-UHFFFAOYSA-N 1,1'-biphenyl;boric acid Chemical compound OB(O)O.C1=CC=CC=C1C1=CC=CC=C1 ANQSYQOHGAJRKN-UHFFFAOYSA-N 0.000 description 1
- XLOVPKCQAPHUKK-UHFFFAOYSA-N 1,2,3,4,4a,5,8,8a-octahydronaphthalene Chemical compound C1C=CCC2CCCCC21 XLOVPKCQAPHUKK-UHFFFAOYSA-N 0.000 description 1
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- ZPQOPVIELGIULI-UHFFFAOYSA-N 1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1 ZPQOPVIELGIULI-UHFFFAOYSA-N 0.000 description 1
- UEMGWPRHOOEKTA-UHFFFAOYSA-N 1,3-difluorobenzene Chemical compound FC1=CC=CC(F)=C1 UEMGWPRHOOEKTA-UHFFFAOYSA-N 0.000 description 1
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
- VNBFUGOVQMFIRN-UHFFFAOYSA-N 1-chlorobutan-2-ol Chemical compound CCC(O)CCl VNBFUGOVQMFIRN-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 description 1
- VQSJAWPFQCXIOB-VODLGYORSA-N 2,3-dihydroxypropyl [(1r,2r,3s,4r,5r,6s)-2,3,6-trihydroxy-4,5-diphosphonooxycyclohexyl] hydrogen phosphate Chemical compound OCC(O)COP(O)(=O)O[C@@H]1[C@H](O)[C@H](O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H]1O VQSJAWPFQCXIOB-VODLGYORSA-N 0.000 description 1
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- KWVPFECTOKLOBL-KTKRTIGZSA-N 2-[(z)-octadec-9-enoxy]ethanol Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCO KWVPFECTOKLOBL-KTKRTIGZSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- BHAKRVSCGILCEW-UHFFFAOYSA-N 2-chloro-4-methylpyrimidine Chemical class CC1=CC=NC(Cl)=N1 BHAKRVSCGILCEW-UHFFFAOYSA-N 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
- 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- XLZYKTYMLBOINK-UHFFFAOYSA-N 3-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)C=2C=CC(O)=CC=2)=C1 XLZYKTYMLBOINK-UHFFFAOYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical group C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-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
- KJFFNMTZQPXCSY-UHFFFAOYSA-N 4-benzyl-5-iodo-6-methyl-1H-pyrimidine-2,4-diamine Chemical class C(C1=CC=CC=C1)C1(NC(=NC(=C1I)C)N)N KJFFNMTZQPXCSY-UHFFFAOYSA-N 0.000 description 1
- VPDWPVXWBVISGS-UHFFFAOYSA-N 4-benzyl-6-methyl-1H-pyrimidine-2,4-diamine Chemical class C(C1=CC=CC=C1)C1(NC(=NC(=C1)C)N)N VPDWPVXWBVISGS-UHFFFAOYSA-N 0.000 description 1
- RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
- CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- SNZSSCZJMVIOCR-UHFFFAOYSA-N 7-azabicyclo[2.2.1]heptane Chemical compound C1CC2CCC1N2 SNZSSCZJMVIOCR-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 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
- SZCZDSRYTNGUCJ-QPJJXVBHSA-N C/C(/N(C)C)=N\C(N)=S Chemical compound C/C(/N(C)C)=N\C(N)=S SZCZDSRYTNGUCJ-QPJJXVBHSA-N 0.000 description 1
- UYRUWCABVUUFME-UHFFFAOYSA-O CC(N(C)C)=NC([NH3+])SC Chemical compound CC(N(C)C)=NC([NH3+])SC UYRUWCABVUUFME-UHFFFAOYSA-O 0.000 description 1
- GYIRYQBREBFQOD-UHFFFAOYSA-N CCN(C(C=C1)=O)c2c1c(C)nc(N)n2 Chemical compound CCN(C(C=C1)=O)c2c1c(C)nc(N)n2 GYIRYQBREBFQOD-UHFFFAOYSA-N 0.000 description 1
- XGGDKQNBRWZINE-UHFFFAOYSA-N CCN(c1c(C=C2Br)c(C)nc(N)n1)C2=O Chemical compound CCN(c1c(C=C2Br)c(C)nc(N)n1)C2=O XGGDKQNBRWZINE-UHFFFAOYSA-N 0.000 description 1
- CVSUURSYHIRNBN-UHFFFAOYSA-N CCNC1=NC(C)(C)C(C=C(C(N2)=O)Br)C2=N1 Chemical compound CCNC1=NC(C)(C)C(C=C(C(N2)=O)Br)C2=N1 CVSUURSYHIRNBN-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 208000009458 Carcinoma in Situ Diseases 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 208000010126 Chondromatosis Diseases 0.000 description 1
- 208000019591 Chondromyxoid fibroma Diseases 0.000 description 1
- 208000005243 Chondrosarcoma Diseases 0.000 description 1
- 201000009047 Chordoma Diseases 0.000 description 1
- 206010048832 Colon adenoma Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 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 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
- 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
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
- 235000002723 Dioscorea alata Nutrition 0.000 description 1
- 235000007056 Dioscorea composita Nutrition 0.000 description 1
- 235000009723 Dioscorea convolvulacea Nutrition 0.000 description 1
- 235000005362 Dioscorea floribunda Nutrition 0.000 description 1
- 235000004868 Dioscorea macrostachya Nutrition 0.000 description 1
- 235000005361 Dioscorea nummularia Nutrition 0.000 description 1
- 235000005360 Dioscorea spiculiflora Nutrition 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 208000007033 Dysgerminoma Diseases 0.000 description 1
- 208000000471 Dysplastic Nevus Syndrome Diseases 0.000 description 1
- 206010062805 Dysplastic naevus Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 201000009051 Embryonal Carcinoma Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010014967 Ependymoma Diseases 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 206010053717 Fibrous histiocytoma Diseases 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 206010018404 Glucagonoma Diseases 0.000 description 1
- 241000197195 Gonioma <angiosperm> Species 0.000 description 1
- 208000002927 Hamartoma Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 235000006350 Ipomoea batatas var. batatas Nutrition 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- 206010023330 Keloid scar Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Natural products OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
- 102000001621 Mucoproteins Human genes 0.000 description 1
- 108010093825 Mucoproteins Proteins 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- XUYPXLNMDZIRQH-LURJTMIESA-N N-acetyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC(C)=O XUYPXLNMDZIRQH-LURJTMIESA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 201000004404 Neurofibroma Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 description 1
- 201000010133 Oligodendroglioma Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 208000000035 Osteochondroma Diseases 0.000 description 1
- 101150037263 PIP2 gene Proteins 0.000 description 1
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 208000007641 Pinealoma Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 101710113459 RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 208000005678 Rhabdomyoma Diseases 0.000 description 1
- 101100262439 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) UBA2 gene Proteins 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- NSOXQYCFHDMMGV-UHFFFAOYSA-N Tetrakis(2-hydroxypropyl)ethylenediamine Chemical compound CC(O)CN(CC(C)O)CCN(CC(C)O)CC(C)O NSOXQYCFHDMMGV-UHFFFAOYSA-N 0.000 description 1
- 240000006474 Theobroma bicolor Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 description 1
- 102400000015 Vasoactive intestinal peptide Human genes 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000007244 Zea mays Nutrition 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 description 1
- LWZFANDGMFTDAV-BURFUSLBSA-N [(2r)-2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O LWZFANDGMFTDAV-BURFUSLBSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- VMRGDFIZRQWOGN-UHFFFAOYSA-N acetic acid;ethyl prop-2-enoate Chemical compound CC(O)=O.CCOC(=O)C=C VMRGDFIZRQWOGN-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 201000004471 adenofibroma Diseases 0.000 description 1
- 208000002718 adenomatoid tumor Diseases 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 125000005084 alkoxyalkylaminoalkyl group Chemical group 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 238000003016 alphascreen Methods 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 229910000329 aluminium sulfate Inorganic materials 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- 125000002393 azetidinyl group Chemical group 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
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 description 1
- 230000002902 bimodal effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012867 bioactive agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 201000002143 bronchus adenoma Diseases 0.000 description 1
- RODCZGBQVPTRTI-UHFFFAOYSA-N but-1-en-2-yl(tributyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C(=C)CC RODCZGBQVPTRTI-UHFFFAOYSA-N 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 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
- 238000004422 calculation algorithm Methods 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000013626 chemical specie Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 201000005217 chondroblastoma Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- NQBWNECTZUOWID-QSYVVUFSSA-N cinnamyl cinnamate Chemical compound C=1C=CC=CC=1\C=C/C(=O)OC\C=C\C1=CC=CC=C1 NQBWNECTZUOWID-QSYVVUFSSA-N 0.000 description 1
- 125000000259 cinnolinyl group Chemical class N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 208000009060 clear cell adenocarcinoma Diseases 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000002508 compound effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 125000004188 dichlorophenyl group Chemical group 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 125000004212 difluorophenyl group Chemical group 0.000 description 1
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- 125000005805 dimethoxy phenyl group Chemical group 0.000 description 1
- 235000004879 dioscorea Nutrition 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 201000009409 embryonal rhabdomyosarcoma Diseases 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 125000002587 enol group Chemical group 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 238000007046 ethoxylation reaction Methods 0.000 description 1
- HCPOCMMGKBZWSJ-UHFFFAOYSA-N ethyl 3-hydrazinyl-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)NN HCPOCMMGKBZWSJ-UHFFFAOYSA-N 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 150000002194 fatty esters Chemical class 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000011207 functional examination Methods 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 208000015419 gastrin-producing neuroendocrine tumor Diseases 0.000 description 1
- 201000000052 gastrinoma Diseases 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229950006191 gluconic acid Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
- 150000002337 glycosamines Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000021552 granulated sugar Nutrition 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 208000006359 hepatoblastoma Diseases 0.000 description 1
- 125000004475 heteroaralkyl group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 201000000284 histiocytoma Diseases 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 201000004933 in situ carcinoma Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 206010022498 insulinoma Diseases 0.000 description 1
- 210000002570 interstitial cell Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000022013 kidney Wilms tumor Diseases 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 208000003849 large cell carcinoma Diseases 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 235000012204 lemonade/lime carbonate Nutrition 0.000 description 1
- 210000000088 lip Anatomy 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 239000002075 main ingredient Substances 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
- 230000007257 malfunction Effects 0.000 description 1
- 201000000289 malignant teratoma Diseases 0.000 description 1
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012907 medicinal substance Substances 0.000 description 1
- 229910000474 mercury oxide Inorganic materials 0.000 description 1
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 230000007483 microbial process Effects 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 208000009091 myxoma Diseases 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 201000008026 nephroblastoma Diseases 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 208000004649 neutrophil actin dysfunction Diseases 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 208000003388 osteoid osteoma Diseases 0.000 description 1
- 208000008798 osteoma Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000005968 oxazolinyl group Chemical group 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 208000021255 pancreatic insulinoma Diseases 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000000505 pernicious effect Effects 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
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 150000003911 phosphatidylinositol 4-phosphates Chemical class 0.000 description 1
- 150000003905 phosphatidylinositols Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 238000003566 phosphorylation assay Methods 0.000 description 1
- 208000024724 pineal body neoplasm Diseases 0.000 description 1
- 201000004123 pineal gland cancer Diseases 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 230000001855 preneoplastic effect Effects 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- 208000029340 primitive neuroectodermal tumor Diseases 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- FKRCODPIKNYEAC-UHFFFAOYSA-N propionic acid ethyl ester Natural products CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 230000009822 protein phosphorylation Effects 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 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
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000000163 radioactive labelling Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000003340 retarding agent Substances 0.000 description 1
- 210000002830 rete testis Anatomy 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 206010039667 schwannoma Diseases 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000002594 sorbent Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000011067 sorbitan monolaureate Nutrition 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 210000001032 spinal nerve Anatomy 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 210000001543 spongioblast Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 208000001608 teratocarcinoma Diseases 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 201000002131 testis sarcoma Diseases 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- CUPOOAWTRIURFT-UHFFFAOYSA-N thiophene-2-carbonitrile Chemical compound N#CC1=CC=CS1 CUPOOAWTRIURFT-UHFFFAOYSA-N 0.000 description 1
- PCTNAMGLSYHIPL-UHFFFAOYSA-N tin(4+) tetraazide Chemical compound [Sn+4].[N-]=[N+]=[N-].[N-]=[N+]=[N-].[N-]=[N+]=[N-].[N-]=[N+]=[N-] PCTNAMGLSYHIPL-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 208000022271 tubular adenoma Diseases 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000004218 vascular function Effects 0.000 description 1
- 230000028973 vesicle-mediated transport Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Obesity (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Neurosurgery (AREA)
- Gastroenterology & Hepatology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US72457105P | 2005-10-07 | 2005-10-07 | |
| US60/724,571 | 2005-10-07 | ||
| US74371906P | 2006-03-23 | 2006-03-23 | |
| US60/743,719 | 2006-03-23 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006800370996A Division CN101395155A (zh) | 2005-10-07 | 2006-10-09 | PI3Kα的吡啶并嘧啶酮抑制剂 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102746298A true CN102746298A (zh) | 2012-10-24 |
Family
ID=37685247
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012102106887A Pending CN102746298A (zh) | 2005-10-07 | 2006-10-09 | PI3Kα的吡啶并嘧啶酮抑制剂 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US8247408B2 (enExample) |
| EP (1) | EP1931670B1 (enExample) |
| JP (4) | JP5480503B2 (enExample) |
| CN (1) | CN102746298A (enExample) |
| AU (1) | AU2006302148B2 (enExample) |
| CA (1) | CA2624965A1 (enExample) |
| EA (1) | EA201200669A1 (enExample) |
| PT (1) | PT1940839E (enExample) |
| WO (1) | WO2007044698A1 (enExample) |
| ZA (1) | ZA200802585B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114394966A (zh) * | 2016-08-15 | 2022-04-26 | 辉瑞公司 | 吡啶并嘧啶酮cdk2/4/6抑制剂 |
Families Citing this family (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8247408B2 (en) * | 2005-10-07 | 2012-08-21 | Exelixis, Inc. | Pyridopyrimidinone inhibitors of PI3Kα for the treatment of cancer |
| EP1931645B1 (en) * | 2005-10-07 | 2014-07-16 | Exelixis, Inc. | N- (3-amino-quinoxalin-2-yl) -sulfonamide derivatives and their use as phosphatidylinositol 3-kinase inhibitors |
| KR20140105621A (ko) * | 2005-10-07 | 2014-09-01 | 엑셀리시스, 인코포레이티드 | ＰＩ３Ｋα의 피리도피리미디논 억제제 |
| AU2007284562B2 (en) | 2006-08-16 | 2013-05-02 | Exelixis, Inc. | Using PI3K and MEK modulators in treatments of cancer |
| MX2009002927A (es) * | 2006-09-15 | 2009-03-31 | Pfizer Prod Inc | Compuestos de pirido (2,3-d)pirimidinona y su uso como inhibidores de la enzima fosfoinositido 3. |
| KR101626435B1 (ko) * | 2007-04-10 | 2016-06-01 | 엑셀리시스, 인코포레이티드 | Ｐｉ３ｋ 알파의 피리도피리미디논 억제제를 이용한 암 치료 방법 |
| WO2008127678A1 (en) * | 2007-04-11 | 2008-10-23 | Exelixis, Inc. | Pyrido [2, 3-d] pyrimidin-7-one compounds as inhibitors of pi3k-alpha for the treatment of cancer |
| CN101711249A (zh) * | 2007-04-11 | 2010-05-19 | 埃克塞里艾克西斯公司 | 作为PI3K-α的抑制剂用于治疗癌症的吡啶并[2,3-D]嘧啶-7-酮化合物 |
| WO2009017838A2 (en) * | 2007-08-01 | 2009-02-05 | Exelixis, Inc. | Combinations of jak-2 inhibitors and other agents |
| EP2350070A1 (en) * | 2008-09-30 | 2011-08-03 | Exelixis, Inc. | Pyridopyrimidinone inhibitors of pi3k and mtor |
| TWI378933B (en) | 2008-10-14 | 2012-12-11 | Daiichi Sankyo Co Ltd | Morpholinopurine derivatives |
| EP2367826A4 (en) | 2008-11-06 | 2012-07-04 | Astrazeneca Ab | MODULATORS OF THE PROTEIN -AMYLOID |
| KR101754664B1 (ko) | 2009-12-18 | 2017-07-06 | 템플 유니버시티-오브 더 커먼웰쓰 시스템 오브 하이어 에듀케이션 | 치환된 피리도〔2,3-ｄ〕피리미딘-7(8ｈ)-온스 및 이의 치료 용도 |
| MX2012009030A (es) | 2010-02-03 | 2012-09-12 | Signal Pharm Llc | Identificacion de mutacion lkb1 como biomarcador predictivo para sensibilidad a inhibidores de tor cinasa. |
| UY33221A (es) | 2010-02-09 | 2011-09-30 | Univ California | MÉTODOS PARA TRATAR CÁNCER USANDO INHIBIDORES DE PI3K Y mTOR EN COMBINACIÓN CON INHIBIDORES DE AUTOFAGIA |
| EA022527B1 (ru) * | 2010-08-05 | 2016-01-29 | Темпл Юниверсити - Оф Дзе Коммонвелт Систем Оф Хайер Эдьюкейшн | 2-ЗАМЕЩЕННЫЕ-8-АЛКИЛ-7-ОКСО-7,8-ДИГИДРОПИРИДО[2,3-d]ПИРИМИДИН-6-КАРБОНИТРИЛЫ И ИХ ПРИМЕНЕНИЕ |
| AU2011302196B2 (en) | 2010-09-14 | 2016-04-28 | Exelixis, Inc. | Inhibitors of PI3K-delta and methods of their use and manufacture |
| WO2012065019A2 (en) * | 2010-11-12 | 2012-05-18 | Exelixis, Inc. | Pyridopyrimidinone inhibitors of p13k alpha |
| WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
| MX2014001246A (es) | 2011-08-03 | 2014-06-11 | Signal Pharm Llc | Identificación del perfil de la expresión génica como biomarcador predictivo del estatus de lkb1. |
| WO2013067141A1 (en) | 2011-11-01 | 2013-05-10 | Exelixis, Inc. | N- (3- { [ (3- { [2-chloro-5- (methoxy) phenyl] amino} quinoxalin- 2 -yl) amino] sulfonyl} phe nyl) - 2 -methylalaninamide as phosphatidylinositol 3 - kinase inhibitor for the treatment of lymphoproliferative malignancies |
| ES2984771T3 (es) | 2012-06-13 | 2024-10-31 | Incyte Holdings Corp | Compuestos tricíclicos sustituidos como inhibidores de FGFR |
| WO2014026125A1 (en) | 2012-08-10 | 2014-02-13 | Incyte Corporation | Pyrazine derivatives as fgfr inhibitors |
| AU2013203714B2 (en) | 2012-10-18 | 2015-12-03 | Signal Pharmaceuticals, Llc | Inhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| NZ629411A (en) | 2013-04-17 | 2017-06-30 | Signal Pharm Llc | Treatment of cancer with dihydropyrazino-pyrazines |
| MX374749B (es) | 2013-04-17 | 2025-03-06 | Signal Pharm Llc | Terapia de combinacion que comprende un inhibidor de tor cinasa y un analogo de citidina para tratar cancer. |
| NZ629469A (en) | 2013-04-17 | 2017-05-26 | Signal Pharm Llc | Methods for treating cancer using dihydropyrazino-pyrazine compound combination therapy |
| CA2909579A1 (en) | 2013-04-17 | 2014-10-23 | Signal Pharmaceuticals, Llc | Combination therapy comprising a tor kinase inhibitor and n-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide for treating cancer |
| NZ629230A (en) | 2013-04-17 | 2017-05-26 | Signal Pharm Llc | Pharmaceutical formulations, processes, solid forms and methods of use relating to 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one |
| EP2986322A1 (en) | 2013-04-17 | 2016-02-24 | Signal Pharmaceuticals, LLC | Combination therapy comprising a tor kinase inhibitor and a 5-substituted quinazolinone compound for treating cancer |
| NZ629332A (en) | 2013-04-17 | 2017-05-26 | Signal Pharm Llc | Treatment of cancer with dihydropyrazino-pyrazines |
| EA035095B1 (ru) | 2013-04-19 | 2020-04-27 | Инсайт Холдингс Корпорейшн | Бициклические гетероциклы в качестве ингибиторов fgfr |
| HK1223286A1 (zh) | 2013-05-29 | 2017-07-28 | 西格诺药品有限公司 | 7-(6-(2-羟基丙-2-基)吡啶-3-基)-1-((反式)-4-甲氧基环己基)-3，4-二氢吡嗪并[2，3-b]吡嗪-2(1h)-酮的药物组合物、其固体形式及它们的使用方法 |
| EP2813504A1 (en) * | 2013-06-14 | 2014-12-17 | Institut Quimic De Sarriá Cets, Fundació Privada | 4-Amino-6-(2,6-dichlorophenyl)-2-(phenylamino)-pyrido[2,3-d]pyrimidin-7(8H)-one derivatives, synthesis and uses thereof |
| EP3131551A4 (en) | 2014-04-16 | 2017-09-20 | Signal Pharmaceuticals, LLC | SOLID FORMS COMPRISING 1-ETHYL-7-(2-METHYL-6-(1H-1,2,4-TRIAZOL-3-YL) PYRIDIN-3-YL)-3,4-DIHYDROPYRAZINO(2,3-b)PYRAZIN-2(1H)-ONE, AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF |
| NZ714742A (en) | 2014-04-16 | 2017-04-28 | Signal Pharm Llc | Solid forms of 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, compositions thereof and methods of their use |
| WO2016015597A1 (en) | 2014-07-26 | 2016-02-04 | Sunshine Lake Pharma Co., Ltd. | Compounds as cdk small-molecule inhibitors and uses thereof |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| EA038045B1 (ru) | 2015-02-20 | 2021-06-28 | Инсайт Корпорейшн | Бициклические гетероциклы в качестве ингибиторов fgfr |
| US9580423B2 (en) | 2015-02-20 | 2017-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| US10730878B2 (en) | 2015-07-11 | 2020-08-04 | Advenchen Pharmaceuticals, LLC | Fused quinoline compounds as PI3K/mTOR inhibitors |
| WO2017019429A1 (en) * | 2015-07-27 | 2017-02-02 | Eli Lilly And Company | 7-phenylethylamino-4h-pyrimido[4,5-d][1,3]oxazin-2-one compounds and theit use as mutant idh1 inhibitors |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| MY198676A (en) | 2017-06-22 | 2023-09-15 | Celgene Corp | Treatment of hepatocellular carcinoma characterized by hepatitis b virus infection |
| RS66310B1 (sr) | 2018-05-04 | 2025-01-31 | Incyte Corp | Čvrsti oblici inhibitora fgfr i procesi za njegovu pripremu |
| US11174257B2 (en) | 2018-05-04 | 2021-11-16 | Incyte Corporation | Salts of an FGFR inhibitor |
| JP7304896B2 (ja) * | 2018-05-21 | 2023-07-07 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | 複素縮合ピリドン化合物及びｉｄｈ阻害剤としてのこれらの使用 |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| WO2021007269A1 (en) | 2019-07-09 | 2021-01-14 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| WO2021067374A1 (en) | 2019-10-01 | 2021-04-08 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| PH12022550892A1 (en) | 2019-10-14 | 2023-05-03 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
| US11697671B2 (en) * | 2019-10-15 | 2023-07-11 | Massachusetts Institute Of Technology | Enhanced crystal nucleation |
| US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| EP4065578A1 (en) | 2019-11-26 | 2022-10-05 | Theravance Biopharma R&D IP, LLC | Fused pyrimidine pyridinone compounds as jak inhibitors |
| AU2020395185A1 (en) | 2019-12-04 | 2022-06-02 | Incyte Corporation | Derivatives of an FGFR inhibitor |
| EP4069696A1 (en) | 2019-12-04 | 2022-10-12 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| US12012409B2 (en) | 2020-01-15 | 2024-06-18 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| JP7549032B2 (ja) * | 2020-03-13 | 2024-09-10 | プロセネスター エルエルシー | ＣＤＫ阻害剤としてのピリド［２，３－ｄ］ピリミジン－７（８Ｈ）－オン |
| JP2024513575A (ja) | 2021-04-12 | 2024-03-26 | インサイト・コーポレイション | Ｆｇｆｒ阻害剤及びネクチン－４標的化剤を含む併用療法 |
| WO2022261160A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| TW202313610A (zh) | 2021-06-09 | 2023-04-01 | 美商英塞特公司 | 作為ｆｇｆｒ抑制劑之三環雜環 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040009993A1 (en) * | 2001-12-11 | 2004-01-15 | Pharmacia Italia S.P.A. | Pyridopyrimidinones derivatives as telomerase inhibitors |
| WO2005105801A1 (en) * | 2004-05-04 | 2005-11-10 | Warner-Lambert Company Llc | Pyrrolyl substituted pyrido[2,3-d]pyrimidin-7-ones and derivatives thereof as therapeutic agents |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL117923A (en) * | 1995-05-03 | 2000-06-01 | Warner Lambert Co | Anti-cancer pharmaceutical compositions containing polysubstituted pyrido¬2,3-d¾pyrimidine derivatives and certain such novel compounds |
| ES2301194T3 (es) * | 1997-02-05 | 2008-06-16 | Warner-Lambert Company Llc | Pirido 2,3-d pirimidinas y 4-aminopirimidinas como inhibidores de la proliferacion celular. |
| US6498163B1 (en) | 1997-02-05 | 2002-12-24 | Warner-Lambert Company | Pyrido[2,3-D]pyrimidines and 4-aminopyrimidines as inhibitors of cellular proliferation |
| GB9904932D0 (en) | 1999-03-04 | 1999-04-28 | Glaxo Group Ltd | Composition and method for preventing/reducing the severity of side effects of chemotherapy and/or radiation therapy |
| EP1255755A1 (en) | 2000-01-27 | 2002-11-13 | Warner-Lambert Company | Pyridopyrimidinone derivatives for treatment of neurodegenerative disease |
| DZ3308A1 (fr) * | 2000-03-06 | 2001-09-27 | Warner Lambert Co | Inhibiteurs de tyrosine kinase a base de 5-alkylpyrido [2,3-d] pyrimidines |
| WO2001083456A1 (en) * | 2000-04-27 | 2001-11-08 | Yamanouchi Pharmaceutical Co., Ltd. | Condensed heteroaryl derivatives |
| EP1364950A4 (en) | 2001-02-26 | 2005-03-09 | Tanabe Seiyaku Co | Pyridopyrimidine and naphthyridine derivatives |
| GEP20063909B (en) * | 2002-01-22 | 2006-08-25 | Warner Lambert Co | 2-(PYRIDIN-2-YLAMINO)-PYRIDO[2,3d] PYRIMIDIN-7-ONES |
| US6822097B1 (en) * | 2002-02-07 | 2004-11-23 | Amgen, Inc. | Compounds and methods of uses |
| PL373339A1 (en) | 2002-04-19 | 2005-08-22 | Smithkline Beecham Corporation | Novel compounds |
| US20040063658A1 (en) | 2002-05-06 | 2004-04-01 | Roberts Christopher Don | Nucleoside derivatives for treating hepatitis C virus infection |
| JP2004083587A (ja) | 2002-08-06 | 2004-03-18 | Tanabe Seiyaku Co Ltd | 医薬組成物 |
| WO2004063195A1 (en) * | 2003-01-03 | 2004-07-29 | Sloan-Kettering Institute For Cancer Research | Pyridopyrimidine kinase inhibitors |
| WO2004089930A1 (en) | 2003-04-02 | 2004-10-21 | Imclone Systems Incorporated | 4-fluoroquinolone derivatives and their use as kinase inhibitors |
| US20070053831A1 (en) | 2003-05-20 | 2007-03-08 | Barrio Jorge R | Methods for binding agents to b-amyloid plaques |
| ATE412650T1 (de) * | 2003-07-11 | 2008-11-15 | Warner Lambert Co | Isethionat salz eines selektiven cdk4 inhibitors |
| US7160888B2 (en) | 2003-08-22 | 2007-01-09 | Warner Lambert Company Llc | [1,8]naphthyridin-2-ones and related compounds for the treatment of schizophrenia |
| EP1718645A1 (en) | 2004-02-18 | 2006-11-08 | Warner-Lambert Company LLC | 2-(pyridin-3-ylamino)-pyrido 2,3-d pyrimidin-7-ones |
| EP1740184A1 (en) * | 2004-03-30 | 2007-01-10 | Pfizer Products Incorporated | Combinations of signal transduction inhibitors |
| WO2005105097A2 (en) | 2004-04-28 | 2005-11-10 | Gpc Biotech Ag | Pyridopyrimidines for treating inflammatory and other diseases |
| EP1761281A1 (en) * | 2004-06-04 | 2007-03-14 | Pfizer Products Incorporated | Method for treating abnormal cell growth |
| JP2008510770A (ja) | 2004-08-26 | 2008-04-10 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｐｌｋ阻害剤としての新規プテリジノン |
| US7608594B2 (en) | 2004-11-03 | 2009-10-27 | University Of Kansas | Novobiocin analogues as anticancer agents |
| JP5111113B2 (ja) | 2004-12-13 | 2012-12-26 | サネシス ファーマシューティカルズ， インコーポレイテッド | Ｒａｆキナーゼ阻害剤として有用なピリドピリミジノン、ジヒドロピリミドピリミジノンおよびプテリジノン |
| US20060142312A1 (en) * | 2004-12-23 | 2006-06-29 | Pfizer Inc | C6-aryl and heteroaryl substituted pyrido[2,3-D] pyrimidin-7-ones |
| US8247408B2 (en) * | 2005-10-07 | 2012-08-21 | Exelixis, Inc. | Pyridopyrimidinone inhibitors of PI3Kα for the treatment of cancer |
| KR20140105621A (ko) * | 2005-10-07 | 2014-09-01 | 엑셀리시스, 인코포레이티드 | ＰＩ３Ｋα의 피리도피리미디논 억제제 |
-
2006
- 2006-10-09 US US11/988,859 patent/US8247408B2/en not_active Expired - Fee Related
- 2006-10-09 EA EA201200669A patent/EA201200669A1/ru unknown
- 2006-10-09 WO PCT/US2006/039472 patent/WO2007044698A1/en not_active Ceased
- 2006-10-09 CN CN2012102106887A patent/CN102746298A/zh active Pending
- 2006-10-09 PT PT68257682T patent/PT1940839E/pt unknown
- 2006-10-09 AU AU2006302148A patent/AU2006302148B2/en not_active Ceased
- 2006-10-09 CA CA002624965A patent/CA2624965A1/en not_active Abandoned
- 2006-10-09 JP JP2008534767A patent/JP5480503B2/ja not_active Expired - Fee Related
- 2006-10-09 EP EP06825665A patent/EP1931670B1/en active Active
-
2008
- 2008-03-20 ZA ZA200802585A patent/ZA200802585B/xx unknown
-
2012
- 2012-12-05 JP JP2012266682A patent/JP2013079255A/ja not_active Withdrawn
-
2014
- 2014-06-18 JP JP2014125567A patent/JP6043754B2/ja not_active Expired - Fee Related
-
2015
- 2015-12-11 JP JP2015242504A patent/JP2016106088A/ja active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040009993A1 (en) * | 2001-12-11 | 2004-01-15 | Pharmacia Italia S.P.A. | Pyridopyrimidinones derivatives as telomerase inhibitors |
| WO2005105801A1 (en) * | 2004-05-04 | 2005-11-10 | Warner-Lambert Company Llc | Pyrrolyl substituted pyrido[2,3-d]pyrimidin-7-ones and derivatives thereof as therapeutic agents |
Non-Patent Citations (1)
| Title |
|---|
| SYLVESTERR.KLUTCHKO, ET AL.: "2-Substituted Aminopyrido[2,3-d]pyrimidin-7(8H)-ones.Structure Activity Relationships Against Selected Tyrosine Kinasesandin Vitroandin Vivo Anticancer Activity", 《J.MED.CHEM.》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114394966A (zh) * | 2016-08-15 | 2022-04-26 | 辉瑞公司 | 吡啶并嘧啶酮cdk2/4/6抑制剂 |
Also Published As
| Publication number | Publication date |
|---|---|
| JP6043754B2 (ja) | 2016-12-14 |
| JP2013079255A (ja) | 2013-05-02 |
| ZA200802585B (en) | 2009-02-25 |
| WO2007044698A1 (en) | 2007-04-19 |
| JP5480503B2 (ja) | 2014-04-23 |
| EP1931670B1 (en) | 2012-09-12 |
| US20090062274A1 (en) | 2009-03-05 |
| JP2016106088A (ja) | 2016-06-16 |
| US8247408B2 (en) | 2012-08-21 |
| CA2624965A1 (en) | 2007-04-19 |
| AU2006302148B2 (en) | 2012-12-06 |
| AU2006302148A1 (en) | 2007-04-19 |
| EA201200669A1 (ru) | 2012-11-30 |
| JP2014221778A (ja) | 2014-11-27 |
| EP1931670A1 (en) | 2008-06-18 |
| PT1940839E (pt) | 2013-10-10 |
| HK1119696A1 (en) | 2009-03-13 |
| JP2009511498A (ja) | 2009-03-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102746298A (zh) | PI3Kα的吡啶并嘧啶酮抑制剂 | |
| EP2322523B1 (en) | Process for the preparation of Pyridopyrimidinone Inhibitors of PI3Kalpha | |
| KR102478614B1 (ko) | 염증 질환의 치료를 위한 신규의 염 및 그의 약학 조성물 | |
| WO2012065019A2 (en) | Pyridopyrimidinone inhibitors of p13k alpha | |
| CN102727498A (zh) | 使用吡啶并嘧啶酮PI3Kα抑制剂的治疗方法 | |
| TWI364415B (en) | Amide derivatives | |
| AU2013200931B2 (en) | Pyridopyrimidinone inhibitors of PI3K alpha | |
| HK1119699B (en) | Pyridopyrimidinone inhibitors of pi3kalpha | |
| HK1161228B (en) | Process for the preparation of pyridopyrimidinone inhibitors of pi3kalpha | |
| HK1161228A (en) | Process for the preparation of pyridopyrimidinone inhibitors of pi3kalpha | |
| HK1119696B (en) | Pyridopyrimidinone inhibitors of pi3k |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20121024 |