HUP0303698A2 - Ciklin dependens kináz inhibitor N-[5-{[(5-alkil-2-oxazolil)-metil]-tio}-2-tiazolil]-karboxamid származékok, alkalmazásuk és ezeket tartalmazó gyógyszerkészítmények - Google Patents

Info

Publication number

HUP0303698A2

HUP0303698A2 HU0303698A HUP0303698A HUP0303698A2 HU P0303698 A2 HUP0303698 A2 HU P0303698A2 HU 0303698 A HU0303698 A HU 0303698A HU P0303698 A HUP0303698 A HU P0303698A HU P0303698 A2 HUP0303698 A2 HU P0303698A2

Authority

HU

Hungary

Prior art keywords

compounds

pharmaceutically acceptable

tert

oxazolyl

thio

Prior art date

2000-07-26

Links

• Espacenet
• Global Dossier
• Discuss

• 239000008194 pharmaceutical composition Substances 0.000 title claims description 31
• 102000003903 Cyclin-dependent kinases Human genes 0.000 title claims description 4
• 108090000266 Cyclin-dependent kinases Proteins 0.000 title claims description 4
• 239000003112 inhibitor Substances 0.000 title description 6
• 150000001875 compounds Chemical class 0.000 claims description 152
• 239000000203 mixture Substances 0.000 claims description 95
• -1 5-tert-butyl-2-oxazolyl Chemical group 0.000 claims description 82
• 150000003839 salts Chemical class 0.000 claims description 76
• 238000002360 preparation method Methods 0.000 claims description 51
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 46
• 125000000217 alkyl group Chemical group 0.000 claims description 41
• 150000003840 hydrochlorides Chemical class 0.000 claims description 27
• SXDBWCPKPHAZSM-UHFFFAOYSA-M bromate Chemical class [O-]Br(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-M 0.000 claims description 26
• 150000001860 citric acid derivatives Chemical class 0.000 claims description 26
• VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 claims description 26
• ICIWUVCWSCSTAQ-UHFFFAOYSA-N iodic acid Chemical class OI(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-N 0.000 claims description 26
• 150000002688 maleic acid derivatives Chemical class 0.000 claims description 26
• AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims description 26
• 150000003890 succinate salts Chemical class 0.000 claims description 26
• 150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 26
• 150000003892 tartrate salts Chemical class 0.000 claims description 26
• 238000011282 treatment Methods 0.000 claims description 23
• 229910052739 hydrogen Inorganic materials 0.000 claims description 22
• 239000001257 hydrogen Substances 0.000 claims description 22
• OUSFTKFNBAZUKL-UHFFFAOYSA-N N-(5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-1,3-thiazol-2-yl)piperidine-4-carboxamide Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)C1CCNCC1 OUSFTKFNBAZUKL-UHFFFAOYSA-N 0.000 claims description 20
• 239000012453 solvate Substances 0.000 claims description 20
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 19
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 13
• 230000002401 inhibitory effect Effects 0.000 claims description 12
• 201000010099 disease Diseases 0.000 claims description 11
• 241000124008 Mammalia Species 0.000 claims description 10
• 206010028980 Neoplasm Diseases 0.000 claims description 10
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 10
• 201000011510 cancer Diseases 0.000 claims description 6
• 102000001253 Protein Kinase Human genes 0.000 claims description 5
• 206010003246 arthritis Diseases 0.000 claims description 5
• 238000002512 chemotherapy Methods 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 230000002062 proliferating effect Effects 0.000 claims description 5
• 108060006633 protein kinase Proteins 0.000 claims description 5
• 101150012716 CDK1 gene Proteins 0.000 claims description 4
• 101100005789 Caenorhabditis elegans cdk-4 gene Proteins 0.000 claims description 4
• 101100059559 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) nimX gene Proteins 0.000 claims description 4
• 101100273808 Xenopus laevis cdk1-b gene Proteins 0.000 claims description 4
• 239000002246 antineoplastic agent Substances 0.000 claims description 4
• 230000006907 apoptotic process Effects 0.000 claims description 4
• 101150073031 cdk2 gene Proteins 0.000 claims description 4
• BMJRSDXYHRHHKI-UHFFFAOYSA-N n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-cyclopropylpiperidine-4-carboxamide Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)C1CCN(C2CC2)CC1 BMJRSDXYHRHHKI-UHFFFAOYSA-N 0.000 claims description 4
• USAKOZCUIYTREA-UHFFFAOYSA-N n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-3-carboxamide Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)C1CNCCC1 USAKOZCUIYTREA-UHFFFAOYSA-N 0.000 claims description 4
• 101150053721 Cdk5 gene Proteins 0.000 claims description 3
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
• MFPWMKHFMBARRG-HAQNSBGRSA-N chembl49618 Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)[C@@H]1CC[C@@H](N)CC1 MFPWMKHFMBARRG-HAQNSBGRSA-N 0.000 claims description 3
• 238000009472 formulation Methods 0.000 claims description 3
• LURBGHNXFQSPMM-UHFFFAOYSA-N n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-(2,3-dihydroxypropyl)piperidine-4-carboxamide Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)C1CCN(CC(O)CO)CC1 LURBGHNXFQSPMM-UHFFFAOYSA-N 0.000 claims description 3
• NASKBLMGBFRGIF-UHFFFAOYSA-N n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-(2-hydroxyethyl)piperidine-4-carboxamide Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)C1CCN(CCO)CC1 NASKBLMGBFRGIF-UHFFFAOYSA-N 0.000 claims description 3
• 230000002265 prevention Effects 0.000 claims description 3
• USAKOZCUIYTREA-LLVKDONJSA-N (3r)-n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-3-carboxamide Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)[C@H]1CNCCC1 USAKOZCUIYTREA-LLVKDONJSA-N 0.000 claims description 2
• USAKOZCUIYTREA-NSHDSACASA-N (3s)-n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-3-carboxamide Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)[C@@H]1CNCCC1 USAKOZCUIYTREA-NSHDSACASA-N 0.000 claims description 2
• 108091007914 CDKs Proteins 0.000 claims description 2
• 101150090188 Cdk8 gene Proteins 0.000 claims description 2
• 206010028116 Mucosal inflammation Diseases 0.000 claims description 2
• 201000010927 Mucositis Diseases 0.000 claims description 2
• 101150112625 SSN3 gene Proteins 0.000 claims description 2
• 101100150415 Schizosaccharomyces pombe (strain 972 / ATCC 24843) srb10 gene Proteins 0.000 claims description 2
• 101150059448 cdk7 gene Proteins 0.000 claims description 2
• RHJVIGLEIFVHIJ-UHFFFAOYSA-N cyclohexanecarboxamide Chemical compound NC(=O)C1[CH]CCCC1 RHJVIGLEIFVHIJ-UHFFFAOYSA-N 0.000 claims description 2
• 201000002364 leukopenia Diseases 0.000 claims description 2
• 231100001022 leukopenia Toxicity 0.000 claims description 2
• 210000000056 organ Anatomy 0.000 claims description 2
• 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 claims description 2
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 2
• 206010043554 thrombocytopenia Diseases 0.000 claims description 2
• UJAICWUNNPDCPV-UHFFFAOYSA-N hydron;2,2,2-trifluoroacetic acid;chloride Chemical compound Cl.OC(=O)C(F)(F)F UJAICWUNNPDCPV-UHFFFAOYSA-N 0.000 claims 23
• 241000894007 species Species 0.000 claims 11
• 208000022605 chemotherapy-induced alopecia Diseases 0.000 claims 1
• 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 103
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 73
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 44
• 239000002904 solvent Substances 0.000 description 43
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 42
• 239000002253 acid Substances 0.000 description 42
• 239000000243 solution Substances 0.000 description 42
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
• 239000007787 solid Substances 0.000 description 34
• 238000006243 chemical reaction Methods 0.000 description 33
• 239000011541 reaction mixture Substances 0.000 description 33
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 22
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 21
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• 150000002430 hydrocarbons Chemical class 0.000 description 21
• 229930195733 hydrocarbon Natural products 0.000 description 20
• 150000008282 halocarbons Chemical class 0.000 description 19
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
• 238000001514 detection method Methods 0.000 description 18
• 150000002170 ethers Chemical class 0.000 description 18
• 239000000284 extract Substances 0.000 description 18
• 239000011877 solvent mixture Substances 0.000 description 18
• 150000001408 amides Chemical class 0.000 description 15
• 125000003118 aryl group Chemical group 0.000 description 15
• 238000004128 high performance liquid chromatography Methods 0.000 description 15
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
• 239000003153 chemical reaction reagent Substances 0.000 description 14
• VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 14
• 150000002576 ketones Chemical class 0.000 description 14
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
• 239000002585 base Substances 0.000 description 13
• 150000004820 halides Chemical class 0.000 description 13
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
• YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 12
• 125000005843 halogen group Chemical group 0.000 description 12
• 239000002244 precipitate Substances 0.000 description 12
• 125000006239 protecting group Chemical group 0.000 description 12
• 229910052938 sodium sulfate Inorganic materials 0.000 description 12
• 235000011152 sodium sulphate Nutrition 0.000 description 12
• 150000001298 alcohols Chemical class 0.000 description 11
• 238000000034 method Methods 0.000 description 11
• 235000017557 sodium bicarbonate Nutrition 0.000 description 11
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
• 150000002148 esters Chemical class 0.000 description 10
• 150000002431 hydrogen Chemical class 0.000 description 10
• 239000000741 silica gel Substances 0.000 description 10
• 229910002027 silica gel Inorganic materials 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 125000001072 heteroaryl group Chemical group 0.000 description 9
• 238000002844 melting Methods 0.000 description 9
• 230000008018 melting Effects 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
• 150000007513 acids Chemical class 0.000 description 8
• 150000001412 amines Chemical class 0.000 description 8
• 150000001540 azides Chemical class 0.000 description 8
• 150000001718 carbodiimides Chemical class 0.000 description 8
• 125000004122 cyclic group Chemical group 0.000 description 8
• 239000012024 dehydrating agents‎ Substances 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• 229910052751 metal Inorganic materials 0.000 description 8
• 239000002184 metal Substances 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• 229910052717 sulfur Inorganic materials 0.000 description 8
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 7
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
• 108091000080 Phosphotransferase Proteins 0.000 description 7
• 230000037396 body weight Effects 0.000 description 7
• 239000004312 hexamethylene tetramine Substances 0.000 description 7
• 235000010299 hexamethylene tetramine Nutrition 0.000 description 7
• 229960004011 methenamine Drugs 0.000 description 7
• 102000020233 phosphotransferase Human genes 0.000 description 7
• 239000000047 product Substances 0.000 description 7
• RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical class NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
• UMGDCJDMYOKAJW-UHFFFAOYSA-N aminothiocarboxamide Natural products NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 6
• 239000003638 chemical reducing agent Substances 0.000 description 6
• 238000003818 flash chromatography Methods 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 125000001453 quaternary ammonium group Chemical group 0.000 description 6
• AGGKEGLBGGJEBZ-UHFFFAOYSA-N tetramethylenedisulfotetramine Chemical compound C1N(S2(=O)=O)CN3S(=O)(=O)N1CN2C3 AGGKEGLBGGJEBZ-UHFFFAOYSA-N 0.000 description 6
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 5
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
• UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 5
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
• 125000003545 alkoxy group Chemical group 0.000 description 5
• 239000003054 catalyst Substances 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 150000002500 ions Chemical class 0.000 description 5
• FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical class OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 5
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
• 235000019341 magnesium sulphate Nutrition 0.000 description 5
• 229910052760 oxygen Inorganic materials 0.000 description 5
• 238000001556 precipitation Methods 0.000 description 5
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 5
• 238000006277 sulfonation reaction Methods 0.000 description 5
• 239000011593 sulfur Substances 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
• NXILIHONWRXHFA-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-3-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCCC(C(O)=O)C1 NXILIHONWRXHFA-UHFFFAOYSA-N 0.000 description 4
• DETXZQGDWUJKMO-UHFFFAOYSA-N 2-hydroxymethanesulfonic acid Chemical compound OCS(O)(=O)=O DETXZQGDWUJKMO-UHFFFAOYSA-N 0.000 description 4
• 208000024827 Alzheimer disease Diseases 0.000 description 4
• 102000016736 Cyclin Human genes 0.000 description 4
• 108050006400 Cyclin Proteins 0.000 description 4
• 241000282412 Homo Species 0.000 description 4
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
• 239000005909 Kieselgur Substances 0.000 description 4
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
• 125000001931 aliphatic group Chemical group 0.000 description 4
• 125000002947 alkylene group Chemical group 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 239000007822 coupling agent Substances 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
• 229910052744 lithium Inorganic materials 0.000 description 4
• 230000014759 maintenance of location Effects 0.000 description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
• 239000012074 organic phase Substances 0.000 description 4
• 239000001301 oxygen Substances 0.000 description 4
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
• PJGSXYOJTGTZAV-UHFFFAOYSA-N pinacolone Chemical class CC(=O)C(C)(C)C PJGSXYOJTGTZAV-UHFFFAOYSA-N 0.000 description 4
• 229910052700 potassium Inorganic materials 0.000 description 4
• 239000011591 potassium Substances 0.000 description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 4
• 125000001424 substituent group Chemical group 0.000 description 4
• 150000003585 thioureas Chemical class 0.000 description 4
• 229910052723 transition metal Inorganic materials 0.000 description 4
• 150000003624 transition metals Chemical class 0.000 description 4
• 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 4
• 241000701447 unidentified baculovirus Species 0.000 description 4
• BPDKBTHOMQPYMF-UHFFFAOYSA-N 1-cyclopropylpiperidin-1-ium-4-carboxylate Chemical compound C1CC(C(=O)O)CCN1C1CC1 BPDKBTHOMQPYMF-UHFFFAOYSA-N 0.000 description 3
• QDOQCOOUTPQMKW-UHFFFAOYSA-N 1-propan-2-ylpiperidine-4-carboxylic acid Chemical compound CC(C)N1CCC(C(O)=O)CC1 QDOQCOOUTPQMKW-UHFFFAOYSA-N 0.000 description 3
• KXMRDHPZQHAXML-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)NC1CCC(C(O)=O)CC1 KXMRDHPZQHAXML-UHFFFAOYSA-N 0.000 description 3
• UNUCZJRZFFSFFA-UHFFFAOYSA-N 5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-amine Chemical compound O1C(C(C)(C)C)=CN=C1CSC1=CN=C(N)S1 UNUCZJRZFFSFFA-UHFFFAOYSA-N 0.000 description 3
• 201000004384 Alopecia Diseases 0.000 description 3
• 102000003909 Cyclin E Human genes 0.000 description 3
• 108090000257 Cyclin E Proteins 0.000 description 3
• KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 3
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 150000001336 alkenes Chemical class 0.000 description 3
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 3
• 125000004414 alkyl thio group Chemical group 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 239000007795 chemical reaction product Substances 0.000 description 3
• 239000003795 chemical substances by application Substances 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• 239000013078 crystal Substances 0.000 description 3
• 239000003480 eluent Substances 0.000 description 3
• LUVKHTGJKFFLMR-UHFFFAOYSA-N ethyl 1-propan-2-ylpiperidine-4-carboxylate Chemical compound CCOC(=O)C1CCN(C(C)C)CC1 LUVKHTGJKFFLMR-UHFFFAOYSA-N 0.000 description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
• 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 3
• 239000012458 free base Substances 0.000 description 3
• 208000024963 hair loss Diseases 0.000 description 3
• 230000003676 hair loss Effects 0.000 description 3
• 229910000040 hydrogen fluoride Inorganic materials 0.000 description 3
• 238000010348 incorporation Methods 0.000 description 3
• 229910001629 magnesium chloride Inorganic materials 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 229910052757 nitrogen Inorganic materials 0.000 description 3
• 229960001592 paclitaxel Drugs 0.000 description 3
• LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical class [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 125000004434 sulfur atom Chemical group 0.000 description 3
• RBLREBLSMAKUKA-UHFFFAOYSA-N tert-butyl n-[4-[[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]carbamoyl]cyclohexyl]carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCC1C(=O)NC(S1)=NC=C1SCC1=NC=C(C(C)(C)C)O1 RBLREBLSMAKUKA-UHFFFAOYSA-N 0.000 description 3
• NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 2
• JCNLOYMZPZCMLX-RFVHGSKJSA-N (3r)-n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-3-carboxamide;hydrochloride Chemical compound Cl.O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)[C@H]1CNCCC1 JCNLOYMZPZCMLX-RFVHGSKJSA-N 0.000 description 2
• XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 description 2
• DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 2
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 2
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
• JBKINHFZTVLNEM-UHFFFAOYSA-N 2-bromoethoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCBr JBKINHFZTVLNEM-UHFFFAOYSA-N 0.000 description 2
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
• ARHCLXWELPFVFQ-UHFFFAOYSA-N 5-bromo-1,3-thiazol-2-amine Chemical compound NC1=NC=C(Br)S1 ARHCLXWELPFVFQ-UHFFFAOYSA-N 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• 208000032467 Aplastic anaemia Diseases 0.000 description 2
• 239000004475 Arginine Substances 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• 108010006654 Bleomycin Proteins 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• 201000009030 Carcinoma Diseases 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 2
• VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical group ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• 108010060385 Cyclin B1 Proteins 0.000 description 2
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
• MNQZXJOMYWMBOU-VKHMYHEASA-N D-glyceraldehyde Chemical compound OC[C@@H](O)C=O MNQZXJOMYWMBOU-VKHMYHEASA-N 0.000 description 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical class OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
• 102100032340 G2/mitotic-specific cyclin-B1 Human genes 0.000 description 2
• 206010018364 Glomerulonephritis Diseases 0.000 description 2
• 108010033040 Histones Proteins 0.000 description 2
• 206010061218 Inflammation Diseases 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
• 239000004472 Lysine Substances 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 102000029749 Microtubule Human genes 0.000 description 2
• 108091022875 Microtubule Proteins 0.000 description 2
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• 229930012538 Paclitaxel Natural products 0.000 description 2
• 201000004681 Psoriasis Diseases 0.000 description 2
• 201000000582 Retinoblastoma Diseases 0.000 description 2
• 108050002653 Retinoblastoma protein Proteins 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 150000008065 acid anhydrides Chemical class 0.000 description 2
• 230000010933 acylation Effects 0.000 description 2
• 238000005917 acylation reaction Methods 0.000 description 2
• 125000004423 acyloxy group Chemical group 0.000 description 2
• 229910052783 alkali metal Inorganic materials 0.000 description 2
• 150000001340 alkali metals Chemical class 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• 150000001342 alkaline earth metals Chemical class 0.000 description 2
• 150000004703 alkoxides Chemical class 0.000 description 2
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 239000001099 ammonium carbonate Substances 0.000 description 2
• 235000012501 ammonium carbonate Nutrition 0.000 description 2
• 239000000908 ammonium hydroxide Substances 0.000 description 2
• 239000000010 aprotic solvent Substances 0.000 description 2
• 239000008346 aqueous phase Substances 0.000 description 2
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
• 150000008365 aromatic ketones Chemical class 0.000 description 2
• 235000010323 ascorbic acid Nutrition 0.000 description 2
• 125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 2
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
• 229940092714 benzenesulfonic acid Drugs 0.000 description 2
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 2
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical class N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 2
• 150000001642 boronic acid derivatives Chemical class 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical group [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 230000004663 cell proliferation Effects 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• IBNWGIFHWSUUCL-UHFFFAOYSA-N cyclohexanecarboxamide;hydrochloride Chemical compound Cl.NC(=O)C1CCCCC1 IBNWGIFHWSUUCL-UHFFFAOYSA-N 0.000 description 2
• OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
• 239000000824 cytostatic agent Substances 0.000 description 2
• 231100000433 cytotoxic Toxicity 0.000 description 2
• 239000002254 cytotoxic agent Substances 0.000 description 2
• 230000001472 cytotoxic effect Effects 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• BEFZAMRWPCMWFJ-UHFFFAOYSA-N desoxyepothilone A Natural products O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC=CCC1C(C)=CC1=CSC(C)=N1 BEFZAMRWPCMWFJ-UHFFFAOYSA-N 0.000 description 2
• XOZIUKBZLSUILX-UHFFFAOYSA-N desoxyepothilone B Natural products O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC(C)=CCC1C(C)=CC1=CSC(C)=N1 XOZIUKBZLSUILX-UHFFFAOYSA-N 0.000 description 2
• AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 2
• RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 2
• 229910000071 diazene Inorganic materials 0.000 description 2
• 208000035475 disorder Diseases 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 2
• HESCAJZNRMSMJG-HGYUPSKWSA-N epothilone A Natural products O=C1[C@H](C)[C@H](O)[C@H](C)CCC[C@H]2O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C HESCAJZNRMSMJG-HGYUPSKWSA-N 0.000 description 2
• BEFZAMRWPCMWFJ-QJKGZULSSA-N epothilone C Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C=C/C[C@H]1C(\C)=C\C1=CSC(C)=N1 BEFZAMRWPCMWFJ-QJKGZULSSA-N 0.000 description 2
• XOZIUKBZLSUILX-GIQCAXHBSA-N epothilone D Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C(C)=C/C[C@H]1C(\C)=C\C1=CSC(C)=N1 XOZIUKBZLSUILX-GIQCAXHBSA-N 0.000 description 2
• ZOOODBUHSVUZEM-UHFFFAOYSA-N ethoxymethanedithioic acid Chemical compound CCOC(S)=S ZOOODBUHSVUZEM-UHFFFAOYSA-N 0.000 description 2
• RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 2
• 238000001914 filtration Methods 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 201000005787 hematologic cancer Diseases 0.000 description 2
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
• 150000004677 hydrates Chemical class 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• 229940071870 hydroiodic acid Drugs 0.000 description 2
• 125000001841 imino group Chemical group [H]N=* 0.000 description 2
• 230000004054 inflammatory process Effects 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
• 238000000021 kinase assay Methods 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 239000010410 layer Substances 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 2
• 229960001924 melphalan Drugs 0.000 description 2
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
• 229910000000 metal hydroxide Inorganic materials 0.000 description 2
• 150000004692 metal hydroxides Chemical class 0.000 description 2
• 210000004688 microtubule Anatomy 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• JJJVIPYJUNRQTI-UHFFFAOYSA-N n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-propan-2-ylpiperidine-4-carboxamide Chemical compound C1CN(C(C)C)CCC1C(=O)NC(S1)=NC=C1SCC1=NC=C(C(C)(C)C)O1 JJJVIPYJUNRQTI-UHFFFAOYSA-N 0.000 description 2
• 208000015122 neurodegenerative disease Diseases 0.000 description 2
• 150000002823 nitrates Chemical class 0.000 description 2
• 239000003921 oil Substances 0.000 description 2
• 230000003287 optical effect Effects 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 210000001672 ovary Anatomy 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• 150000003003 phosphines Chemical class 0.000 description 2
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
• UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 210000002307 prostate Anatomy 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 2
• 150000003222 pyridines Chemical class 0.000 description 2
• 238000006722 reduction reaction Methods 0.000 description 2
• 150000003873 salicylate salts Chemical class 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 238000007086 side reaction Methods 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• 201000009890 sinusitis Diseases 0.000 description 2
• 159000000000 sodium salts Chemical class 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 238000003756 stirring Methods 0.000 description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
• 208000024891 symptom Diseases 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
• NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 2
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-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
• IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 2
• VHKIEYIESYMHPT-UHFFFAOYSA-N triethyl(methoxycarbonylsulfamoyl)azanium;hydroxide Chemical compound [OH-].CC[N+](CC)(CC)S(=O)(=O)NC(=O)OC VHKIEYIESYMHPT-UHFFFAOYSA-N 0.000 description 2
• AADVCYNFEREWOS-UHFFFAOYSA-N (+)-DDM Natural products C=CC=CC(C)C(OC(N)=O)C(C)C(O)C(C)CC(C)=CC(C)C(O)C(C)C=CC(O)CC1OC(=O)C(C)C(O)C1C AADVCYNFEREWOS-UHFFFAOYSA-N 0.000 description 1
• BZMMRNKDONDVIB-UHFFFAOYSA-N (1-ethoxycyclopropyl)oxy-trimethylsilane Chemical compound CCOC1(O[Si](C)(C)C)CC1 BZMMRNKDONDVIB-UHFFFAOYSA-N 0.000 description 1
• MCEHFIXEKNKSRW-LBPRGKRZSA-N (2s)-2-[[3,5-dichloro-4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=C(Cl)C=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1Cl MCEHFIXEKNKSRW-LBPRGKRZSA-N 0.000 description 1
• JCNLOYMZPZCMLX-MERQFXBCSA-N (3s)-n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-3-carboxamide;hydrochloride Chemical compound Cl.O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)[C@@H]1CNCCC1 JCNLOYMZPZCMLX-MERQFXBCSA-N 0.000 description 1
• NUSVDASTCPBUIP-UHFFFAOYSA-N (5-bromo-1,3-thiazol-2-yl)azanium;bromide Chemical compound [Br-].BrC1=C[NH2+]C(=N)S1 NUSVDASTCPBUIP-UHFFFAOYSA-N 0.000 description 1
• UCGJDVMPLINVCQ-UHFFFAOYSA-N (5-tert-butyl-1,3-oxazol-2-yl)methyl carbamimidothioate;hydrochloride Chemical compound Cl.CC(C)(C)C1=CN=C(CSC(N)=N)O1 UCGJDVMPLINVCQ-UHFFFAOYSA-N 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
• LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• ORECNKBJIMKZNX-UHFFFAOYSA-N 1,3-thiazol-3-ium;chloride Chemical compound Cl.C1=CSC=N1 ORECNKBJIMKZNX-UHFFFAOYSA-N 0.000 description 1
• SIJJBDAIXLFJRV-UHFFFAOYSA-N 1-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)C1CCN(CCO[Si](C)(C)C(C)(C)C)CC1 SIJJBDAIXLFJRV-UHFFFAOYSA-N 0.000 description 1
• 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 1
• SXFWKZNLYYRHMK-UHFFFAOYSA-N 1h-indolo[7,6-f]quinoline Chemical class C1=CC=C2C3=C(NC=C4)C4=CC=C3C=CC2=N1 SXFWKZNLYYRHMK-UHFFFAOYSA-N 0.000 description 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
• NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
• TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
• DRNGLYHKYPNTEA-UHFFFAOYSA-N 4-azaniumylcyclohexane-1-carboxylate Chemical compound NC1CCC(C(O)=O)CC1 DRNGLYHKYPNTEA-UHFFFAOYSA-N 0.000 description 1
• LUGZUJZYTRPEDY-UHFFFAOYSA-N 5-tert-butyl-2-(chloromethyl)-1,3-oxazole Chemical compound CC(C)(C)C1=CN=C(CCl)O1 LUGZUJZYTRPEDY-UHFFFAOYSA-N 0.000 description 1
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• 206010065040 AIDS dementia complex Diseases 0.000 description 1
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
• 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
• 102400000068 Angiostatin Human genes 0.000 description 1
• 108010079709 Angiostatins Proteins 0.000 description 1
• 108010024976 Asparaginase Proteins 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 208000003950 B-cell lymphoma Diseases 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• IVCJALMAHYOQID-UHFFFAOYSA-N CS(=O)(=O)O.CC(C)(C)C1=CN=C(O1)CSC1=CN=C(S1)NC(=O)C1CCNCC1 Chemical compound CS(=O)(=O)O.CC(C)(C)C1=CN=C(O1)CSC1=CN=C(S1)NC(=O)C1CCNCC1 IVCJALMAHYOQID-UHFFFAOYSA-N 0.000 description 1
• 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
• KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
• 206010058019 Cancer Pain Diseases 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 208000010667 Carcinoma of liver and intrahepatic biliary tract Diseases 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• FJXMJSRZWYAPTQ-GJTSMBTKSA-N Cl.O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)[C@@H]1CC[C@@H](N)CC1 Chemical compound Cl.O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)[C@@H]1CC[C@@H](N)CC1 FJXMJSRZWYAPTQ-GJTSMBTKSA-N 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 102000003910 Cyclin D Human genes 0.000 description 1
• 108090000259 Cyclin D Proteins 0.000 description 1
• 102000013701 Cyclin-Dependent Kinase 4 Human genes 0.000 description 1
• 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 0.000 description 1
• AADVCYNFEREWOS-OBRABYBLSA-N Discodermolide Chemical compound C=C\C=C/[C@H](C)[C@H](OC(N)=O)[C@@H](C)[C@H](O)[C@@H](C)C\C(C)=C/[C@H](C)[C@@H](O)[C@@H](C)\C=C/[C@@H](O)C[C@@H]1OC(=O)[C@H](C)[C@@H](O)[C@H]1C AADVCYNFEREWOS-OBRABYBLSA-N 0.000 description 1
• SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
• 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 1
• 101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 1
• 102000001301 EGF receptor Human genes 0.000 description 1
• 108060006698 EGF receptor Proteins 0.000 description 1
• 102400001047 Endostatin Human genes 0.000 description 1
• 108010079505 Endostatins Proteins 0.000 description 1
• 206010014824 Endotoxic shock Diseases 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• QXRSDHAAWVKZLJ-OXZHEXMSSA-N Epothilone B Natural products O=C1[C@H](C)[C@H](O)[C@@H](C)CCC[C@@]2(C)O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C QXRSDHAAWVKZLJ-OXZHEXMSSA-N 0.000 description 1
• BEFZAMRWPCMWFJ-JRBBLYSQSA-N Epothilone C Natural products O=C1[C@H](C)[C@@H](O)[C@@H](C)CCC/C=C\C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C BEFZAMRWPCMWFJ-JRBBLYSQSA-N 0.000 description 1
• XOZIUKBZLSUILX-SDMHVBBESA-N Epothilone D Natural products O=C1[C@H](C)[C@@H](O)[C@@H](C)CCC/C(/C)=C/C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C XOZIUKBZLSUILX-SDMHVBBESA-N 0.000 description 1
• 201000008808 Fibrosarcoma Diseases 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
• 206010017533 Fungal infection Diseases 0.000 description 1
• 208000032612 Glial tumor Diseases 0.000 description 1
• 206010018338 Glioma Diseases 0.000 description 1
• 206010073069 Hepatic cancer Diseases 0.000 description 1
• 102000006947 Histones Human genes 0.000 description 1
• 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
• 241000243251 Hydra Species 0.000 description 1
• 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
• 102000014150 Interferons Human genes 0.000 description 1
• 108010050904 Interferons Proteins 0.000 description 1
• 102000015696 Interleukins Human genes 0.000 description 1
• 108010063738 Interleukins Proteins 0.000 description 1
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
• 108010000817 Leuprolide Proteins 0.000 description 1
• JXLYSJRDGCGARV-PJXZDTQASA-N Leurosidine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-PJXZDTQASA-N 0.000 description 1
• LPGWZGMPDKDHEP-HLTPFJCJSA-N Leurosine Chemical compound C([C@]1([C@@H]2O1)CC)N(CCC=1C3=CC=CC=C3NC=11)C[C@H]2C[C@]1(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC LPGWZGMPDKDHEP-HLTPFJCJSA-N 0.000 description 1
• LPGWZGMPDKDHEP-GKWAKPNHSA-N Leurosine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@]6(CC)O[C@@H]6[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C LPGWZGMPDKDHEP-GKWAKPNHSA-N 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• 108091054455 MAP kinase family Proteins 0.000 description 1
• 102000043136 MAP kinase family Human genes 0.000 description 1
• 229940124647 MEK inhibitor Drugs 0.000 description 1
• 229930192392 Mitomycin Natural products 0.000 description 1
• 101100268648 Mus musculus Abl1 gene Proteins 0.000 description 1
• 208000031888 Mycoses Diseases 0.000 description 1
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
• 101001055320 Myxine glutinosa Insulin-like growth factor Proteins 0.000 description 1
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 208000009905 Neurofibromatoses Diseases 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 108091008606 PDGF receptors Proteins 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 208000037273 Pathologic Processes Diseases 0.000 description 1
• 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 1
• 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
• 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
• HRHKSTOGXBBQCB-UHFFFAOYSA-N Porfiromycine Chemical compound O=C1C(N)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)C3N(C)C3CN12 HRHKSTOGXBBQCB-UHFFFAOYSA-N 0.000 description 1
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 102000003923 Protein Kinase C Human genes 0.000 description 1
• 108090000315 Protein Kinase C Proteins 0.000 description 1
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
• 206010038389 Renal cancer Diseases 0.000 description 1
• 206010063837 Reperfusion injury Diseases 0.000 description 1
• 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
• 201000010208 Seminoma Diseases 0.000 description 1
• 206010040070 Septic Shock Diseases 0.000 description 1
• 241000710960 Sindbis virus Species 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 229940123237 Taxane Drugs 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
• 208000033781 Thyroid carcinoma Diseases 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 102000004357 Transferases Human genes 0.000 description 1
• 108090000992 Transferases Proteins 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
• 241000863480 Vinca Species 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• JXLYSJRDGCGARV-KSNABSRWSA-N ac1l29ym Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-KSNABSRWSA-N 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 150000001335 aliphatic alkanes Chemical class 0.000 description 1
• 125000005189 alkyl hydroxy group Chemical group 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 229960000473 altretamine Drugs 0.000 description 1
• 229940037003 alum Drugs 0.000 description 1
• 229960003896 aminopterin Drugs 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 239000004037 angiogenesis inhibitor Substances 0.000 description 1
• 238000002399 angioplasty Methods 0.000 description 1
• 229940045799 anthracyclines and related substance Drugs 0.000 description 1
• 230000001093 anti-cancer Effects 0.000 description 1
• 230000003388 anti-hormonal effect Effects 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 230000000259 anti-tumor effect Effects 0.000 description 1
• 238000011394 anticancer treatment Methods 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 239000004599 antimicrobial Substances 0.000 description 1
• 229940076005 apoptosis modulator Drugs 0.000 description 1
• 230000005775 apoptotic pathway Effects 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 150000008209 arabinosides Chemical class 0.000 description 1
• 239000003886 aromatase inhibitor Substances 0.000 description 1
• 229940046844 aromatase inhibitors Drugs 0.000 description 1
• 230000006793 arrhythmia Effects 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
• 238000010533 azeotropic distillation Methods 0.000 description 1
• RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
• 229910001863 barium hydroxide Inorganic materials 0.000 description 1
• ZUDYPQRUOYEARG-UHFFFAOYSA-L barium(2+);dihydroxide;octahydrate Chemical compound O.O.O.O.O.O.O.O.[OH-].[OH-].[Ba+2] ZUDYPQRUOYEARG-UHFFFAOYSA-L 0.000 description 1
• 229960000997 bicalutamide Drugs 0.000 description 1
• 201000001531 bladder carcinoma Diseases 0.000 description 1
• 229960001561 bleomycin Drugs 0.000 description 1
• 238000004820 blood count Methods 0.000 description 1
• 201000008275 breast carcinoma Diseases 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229910052792 caesium Inorganic materials 0.000 description 1
• VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
• 229940127093 camptothecin Drugs 0.000 description 1
• VQXINLNPICQTLR-UHFFFAOYSA-N carbonyl diazide Chemical compound [N-]=[N+]=NC(=O)N=[N+]=[N-] VQXINLNPICQTLR-UHFFFAOYSA-N 0.000 description 1
• 229960004562 carboplatin Drugs 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• XREUEWVEMYWFFA-CSKJXFQVSA-N carminomycin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XREUEWVEMYWFFA-CSKJXFQVSA-N 0.000 description 1
• 229930188550 carminomycin Natural products 0.000 description 1
• XREUEWVEMYWFFA-UHFFFAOYSA-N carminomycin I Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XREUEWVEMYWFFA-UHFFFAOYSA-N 0.000 description 1
• 229950001725 carubicin Drugs 0.000 description 1
• 210000004027 cell Anatomy 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 208000025434 cerebellar degeneration Diseases 0.000 description 1
• 208000019065 cervical carcinoma Diseases 0.000 description 1
• 210000003679 cervix uteri Anatomy 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 238000004296 chiral HPLC Methods 0.000 description 1
• 238000010568 chiral column chromatography Methods 0.000 description 1
• 239000000460 chlorine Substances 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 1
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
• 229960004316 cisplatin Drugs 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 210000002808 connective tissue Anatomy 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 125000004093 cyano group Chemical group *C#N 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 229960000684 cytarabine Drugs 0.000 description 1
• 229940104302 cytosine Drugs 0.000 description 1
• 229940127089 cytotoxic agent Drugs 0.000 description 1
• 231100000599 cytotoxic agent Toxicity 0.000 description 1
• 229960003901 dacarbazine Drugs 0.000 description 1
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
• 229960000975 daunorubicin Drugs 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 150000001993 dienes Chemical class 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
• 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
• 229960003668 docetaxel Drugs 0.000 description 1
• 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 229960004679 doxorubicin Drugs 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 229940088598 enzyme Drugs 0.000 description 1
• YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 1
• 229930013356 epothilone Natural products 0.000 description 1
• QXRSDHAAWVKZLJ-PVYNADRNSA-N epothilone B Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 QXRSDHAAWVKZLJ-PVYNADRNSA-N 0.000 description 1
• FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
• 229960001842 estramustine Drugs 0.000 description 1
• LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 1
• 229960000752 etoposide phosphate Drugs 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
• 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000001605 fetal effect Effects 0.000 description 1
• 239000012065 filter cake Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229960002949 fluorouracil Drugs 0.000 description 1
• MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
• 229960002074 flutamide Drugs 0.000 description 1
• 201000003444 follicular lymphoma Diseases 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 206010017758 gastric cancer Diseases 0.000 description 1
• 208000010749 gastric carcinoma Diseases 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
• 229960005277 gemcitabine Drugs 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 239000003966 growth inhibitor Substances 0.000 description 1
• 230000003394 haemopoietic effect Effects 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 208000014951 hematologic disease Diseases 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• LZWPOLSJFGLQCE-UHFFFAOYSA-N heptadecane-5,9-dione Chemical compound CCCCCCCCC(=O)CCCC(=O)CCCC LZWPOLSJFGLQCE-UHFFFAOYSA-N 0.000 description 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
• UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000013632 homeostatic process Effects 0.000 description 1
• 230000003054 hormonal effect Effects 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
• 230000001969 hypertrophic effect Effects 0.000 description 1
• 239000000367 immunologic factor Substances 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 229940047124 interferons Drugs 0.000 description 1
• 229940047122 interleukins Drugs 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• KLEAIHJJLUAXIQ-JDRGBKBRSA-N irinotecan hydrochloride hydrate Chemical compound O.O.O.Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 KLEAIHJJLUAXIQ-JDRGBKBRSA-N 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([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
• 210000003734 kidney Anatomy 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
• 229960004338 leuprorelin Drugs 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 201000002250 liver carcinoma Diseases 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 238000011068 loading method Methods 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
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 229960001428 mercaptopurine Drugs 0.000 description 1
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• FBOZXECLQNJBKD-UHFFFAOYSA-N methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-UHFFFAOYSA-N 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 description 1
• 229960004857 mitomycin Drugs 0.000 description 1
• KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
• 229960001156 mitoxantrone Drugs 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 239000012452 mother liquor Substances 0.000 description 1
• 210000002346 musculoskeletal system Anatomy 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• JEUXZUSUYIHGNL-UHFFFAOYSA-N n,n-diethylethanamine;hydrate Chemical compound O.CCN(CC)CC JEUXZUSUYIHGNL-UHFFFAOYSA-N 0.000 description 1
• ASWZUYTWTZIVNN-UHFFFAOYSA-N n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide;hydrobromide Chemical compound Br.O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)C1CCNCC1 ASWZUYTWTZIVNN-UHFFFAOYSA-N 0.000 description 1
• PKCYFIUOIGVHLX-UHFFFAOYSA-N n-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide;hydrochloride Chemical compound Cl.O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)C1CCNCC1 PKCYFIUOIGVHLX-UHFFFAOYSA-N 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 201000004931 neurofibromatosis Diseases 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000002777 nucleoside Substances 0.000 description 1
• 125000003835 nucleoside group Chemical group 0.000 description 1
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 239000012044 organic layer Substances 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 201000008968 osteosarcoma Diseases 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000009054 pathological process Effects 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 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
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 238000000053 physical method Methods 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 1
• 229960001237 podophyllotoxin Drugs 0.000 description 1
• YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 1
• 208000015768 polyposis Diseases 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
• 229960000624 procarbazine Drugs 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 201000001514 prostate carcinoma Diseases 0.000 description 1
• CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 201000010174 renal carcinoma Diseases 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 230000037390 scarring Effects 0.000 description 1
• 201000000849 skin cancer Diseases 0.000 description 1
• 201000008261 skin carcinoma Diseases 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 208000002320 spinal muscular atrophy Diseases 0.000 description 1
• 102000009076 src-Family Kinases Human genes 0.000 description 1
• 108010087686 src-Family Kinases Proteins 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 201000000498 stomach carcinoma Diseases 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 239000001384 succinic acid Substances 0.000 description 1
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 229960001603 tamoxifen Drugs 0.000 description 1
• 102000013498 tau Proteins Human genes 0.000 description 1
• 108010026424 tau Proteins Proteins 0.000 description 1
• 229960001278 teniposide Drugs 0.000 description 1
• 208000001608 teratocarcinoma Diseases 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• ZXUCBXRTRRIBSO-UHFFFAOYSA-L tetrabutylazanium;sulfate Chemical compound [O-]S([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC ZXUCBXRTRRIBSO-UHFFFAOYSA-L 0.000 description 1
• 150000003557 thiazoles Chemical class 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• 150000003573 thiols Chemical class 0.000 description 1
• 229960001196 thiotepa Drugs 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• 208000013077 thyroid gland carcinoma Diseases 0.000 description 1
• 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
• 229960000303 topotecan Drugs 0.000 description 1
• 125000004665 trialkylsilyl group Chemical group 0.000 description 1
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
• 229960001099 trimetrexate Drugs 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 241000701161 unidentified adenovirus Species 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 210000003932 urinary bladder Anatomy 0.000 description 1
• 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
• 238000007631 vascular surgery Methods 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 229960003048 vinblastine Drugs 0.000 description 1
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
• 229960004528 vincristine Drugs 0.000 description 1
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
• UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
• 229960004355 vindesine Drugs 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
• 239000003039 volatile agent Substances 0.000 description 1