KR950011740B1 - 축합된 피리미딘 유도체 - Google Patents
축합된 피리미딘 유도체 Download PDFInfo
- Publication number
- KR950011740B1 KR950011740B1 KR1019920015043A KR920015043A KR950011740B1 KR 950011740 B1 KR950011740 B1 KR 950011740B1 KR 1019920015043 A KR1019920015043 A KR 1019920015043A KR 920015043 A KR920015043 A KR 920015043A KR 950011740 B1 KR950011740 B1 KR 950011740B1
- Authority
- KR
- South Korea
- Prior art keywords
- group
- pharmacologically acceptable
- acceptable salt
- pyrimidine derivative
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000003230 pyrimidines Chemical class 0.000 title claims description 58
- 150000001875 compounds Chemical class 0.000 claims description 343
- 239000000203 mixture Substances 0.000 claims description 217
- -1 phenylene, pyridindiyl Chemical group 0.000 claims description 187
- 238000000034 method Methods 0.000 claims description 81
- 150000003839 salts Chemical class 0.000 claims description 78
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 75
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 65
- 125000003277 amino group Chemical group 0.000 claims description 49
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 39
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
- 150000002430 hydrocarbons Chemical group 0.000 claims description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 29
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- 125000005843 halogen group Chemical group 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 125000001118 alkylidene group Chemical group 0.000 claims description 19
- 125000001634 furandiyl group Chemical group O1C(=C(C=C1)*)* 0.000 claims description 19
- KCTZOTUQSGYWLV-UHFFFAOYSA-N N1C=NC=C2N=CC=C21 Chemical class N1C=NC=C2N=CC=C21 KCTZOTUQSGYWLV-UHFFFAOYSA-N 0.000 claims description 13
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 13
- 239000002246 antineoplastic agent Substances 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 229940041181 antineoplastic drug Drugs 0.000 claims description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 claims description 7
- 239000004215 Carbon black (E152) Chemical group 0.000 claims description 6
- 229930195733 hydrocarbon Chemical group 0.000 claims description 6
- BJUPTJXRJDXLHF-UHFFFAOYSA-N 6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical class N1=CN=C2CCCC2=C1 BJUPTJXRJDXLHF-UHFFFAOYSA-N 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 239000000945 filler Substances 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 5
- 125000003262 carboxylic acid ester group Chemical class [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 205
- 238000002360 preparation method Methods 0.000 description 196
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 160
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 159
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 130
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 122
- 239000002904 solvent Substances 0.000 description 118
- 239000000243 solution Substances 0.000 description 117
- 238000006243 chemical reaction Methods 0.000 description 102
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 84
- 238000010898 silica gel chromatography Methods 0.000 description 69
- 239000011541 reaction mixture Substances 0.000 description 65
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 60
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 59
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
- 239000012044 organic layer Substances 0.000 description 55
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 50
- 238000001816 cooling Methods 0.000 description 50
- 235000002639 sodium chloride Nutrition 0.000 description 46
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 42
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
- 239000007864 aqueous solution Substances 0.000 description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 37
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 35
- 229960002989 glutamic acid Drugs 0.000 description 34
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 34
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 32
- 229920006395 saturated elastomer Polymers 0.000 description 31
- 235000019270 ammonium chloride Nutrition 0.000 description 29
- 239000002253 acid Substances 0.000 description 23
- 239000000047 product Substances 0.000 description 23
- 150000002148 esters Chemical class 0.000 description 22
- 238000004519 manufacturing process Methods 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 230000009257 reactivity Effects 0.000 description 21
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 20
- 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 19
- 239000003513 alkali Substances 0.000 description 19
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 18
- 239000011780 sodium chloride Substances 0.000 description 18
- 206010028980 Neoplasm Diseases 0.000 description 17
- 230000008569 process Effects 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 15
- 239000002585 base Substances 0.000 description 15
- 239000000543 intermediate Substances 0.000 description 15
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 15
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 14
- 239000000843 powder Substances 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 13
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- TYDXSUIPFVFLNU-UHFFFAOYSA-N tert-butyl 5-[3-(3-amino-2-cyanopyrrol-1-yl)propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC(C)(C)C)=CC=C1CCCN1C(C#N)=C(N)C=C1 TYDXSUIPFVFLNU-UHFFFAOYSA-N 0.000 description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical class B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 11
- 239000006185 dispersion Substances 0.000 description 11
- 150000003138 primary alcohols Chemical class 0.000 description 11
- 239000012312 sodium hydride Substances 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 108010022394 Threonine synthase Proteins 0.000 description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
- 150000001733 carboxylic acid esters Chemical class 0.000 description 10
- 238000004517 catalytic hydrocracking Methods 0.000 description 10
- 102000004419 dihydrofolate reductase Human genes 0.000 description 10
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 10
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
- WJTWHJRAPTZRNI-UHFFFAOYSA-N 5-oxocyclopentene-1-carbonitrile Chemical compound O=C1CCC=C1C#N WJTWHJRAPTZRNI-UHFFFAOYSA-N 0.000 description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 150000002576 ketones Chemical class 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 150000002306 glutamic acid derivatives Chemical group 0.000 description 8
- 150000007524 organic acids Chemical class 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 238000007239 Wittig reaction Methods 0.000 description 7
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 150000004820 halides Chemical class 0.000 description 7
- 208000032839 leukemia Diseases 0.000 description 7
- DUNFNBQQWYQKFE-UHFFFAOYSA-N tert-butyl 4-formylbenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=C(C=O)C=C1 DUNFNBQQWYQKFE-UHFFFAOYSA-N 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 7
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 6
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 6
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 6
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 229910000085 borane Inorganic materials 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 238000007796 conventional method Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000004052 folic acid antagonist Substances 0.000 description 6
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 5
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 230000003432 anti-folate effect Effects 0.000 description 5
- 229940127074 antifolate Drugs 0.000 description 5
- 239000000010 aprotic solvent Substances 0.000 description 5
- 238000010531 catalytic reduction reaction Methods 0.000 description 5
- 238000009833 condensation Methods 0.000 description 5
- 230000005494 condensation Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 5
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 5
- 150000007530 organic bases Chemical class 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000009518 sodium iodide Nutrition 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 4
- ZKKBIZXAEDFPNL-HWKANZROSA-N (e)-3-(dimethylamino)prop-2-enenitrile Chemical compound CN(C)\C=C\C#N ZKKBIZXAEDFPNL-HWKANZROSA-N 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 4
- ZFFWIOSEDOAZAY-UHFFFAOYSA-N 2-aminoprop-2-enenitrile Chemical compound NC(=C)C#N ZFFWIOSEDOAZAY-UHFFFAOYSA-N 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 4
- 229930194542 Keto Natural products 0.000 description 4
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
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- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical class C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- QBYLSTQGSZWFSK-UHFFFAOYSA-N methyl 5-oxocyclopentene-1-carboxylate Chemical compound COC(=O)C1=CCCC1=O QBYLSTQGSZWFSK-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 150000002762 monocarboxylic acid derivatives Chemical class 0.000 description 1
- CMESPBFFDMPSIY-UHFFFAOYSA-N n,n'-diphenylmethanediimine Chemical compound C1=CC=CC=C1N=C=NC1=CC=CC=C1 CMESPBFFDMPSIY-UHFFFAOYSA-N 0.000 description 1
- MBHINSULENHCMF-UHFFFAOYSA-N n,n-dimethylpropanamide Chemical group CCC(=O)N(C)C MBHINSULENHCMF-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- ZCYXXKJEDCHMGH-UHFFFAOYSA-N nonane Chemical compound CCCC[CH]CCCC ZCYXXKJEDCHMGH-UHFFFAOYSA-N 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
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- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NFBAXHOPROOJAW-UHFFFAOYSA-N phenindione Chemical compound O=C1C2=CC=CC=C2C(=O)C1C1=CC=CC=C1 NFBAXHOPROOJAW-UHFFFAOYSA-N 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- PMOIAJVKYNVHQE-UHFFFAOYSA-N phosphanium;bromide Chemical compound [PH4+].[Br-] PMOIAJVKYNVHQE-UHFFFAOYSA-N 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920001289 polyvinyl ether Polymers 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 125000000075 primary alcohol group Chemical group 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- KJRCEJOSASVSRA-UHFFFAOYSA-N propane-2-thiol Chemical compound CC(C)S KJRCEJOSASVSRA-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical group N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 150000003195 pteridines Chemical class 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- PSHHQIGKVLIVBD-UHFFFAOYSA-N purine-2,4-diamine Chemical compound C1=NC(N)=NC2(N)N=CN=C21 PSHHQIGKVLIVBD-UHFFFAOYSA-N 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003198 secondary alcohol group Chemical group 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000010265 sodium sulphite Nutrition 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
- 239000000600 sorbitol Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical class [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 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 1
- MGZCTASYYGPLOX-UHFFFAOYSA-N tert-butyl 2,4-diamino-6,7-dihydropyrrolo[3,2-d]pyrimidine-5-carboxylate Chemical compound NC1=NC(N)=C2N(C(=O)OC(C)(C)C)CCC2=N1 MGZCTASYYGPLOX-UHFFFAOYSA-N 0.000 description 1
- AMGDHQPXAGWBSF-UHFFFAOYSA-N tert-butyl 2-formylbenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC=C1C=O AMGDHQPXAGWBSF-UHFFFAOYSA-N 0.000 description 1
- PVQNTVHQKYIUSX-UHFFFAOYSA-N tert-butyl 2-formylfuran-3-carboxylate Chemical compound CC(C)(C)OC(=O)C=1C=COC=1C=O PVQNTVHQKYIUSX-UHFFFAOYSA-N 0.000 description 1
- IKKLJXYPOCPKRW-UHFFFAOYSA-N tert-butyl 4-(1-hydroxybut-3-enyl)benzoate Chemical compound CC(C)(C)OC(=O)C1=CC=C(C(O)CC=C)C=C1 IKKLJXYPOCPKRW-UHFFFAOYSA-N 0.000 description 1
- FKQKKUDGXRBBOL-UHFFFAOYSA-N tert-butyl 4-(3-ethoxy-3-oxoprop-1-en-2-yl)benzoate Chemical compound CCOC(=O)C(=C)C1=CC=C(C(=O)OC(C)(C)C)C=C1 FKQKKUDGXRBBOL-UHFFFAOYSA-N 0.000 description 1
- HALAIVCELHMZNX-UHFFFAOYSA-N tert-butyl 4-(3-ethoxy-3-oxopropyl)benzoate Chemical compound CCOC(=O)CCC1=CC=C(C(=O)OC(C)(C)C)C=C1 HALAIVCELHMZNX-UHFFFAOYSA-N 0.000 description 1
- YVRUDIVGJUZATC-UHFFFAOYSA-N tert-butyl 4-(4-bromobutan-2-yl)benzoate Chemical compound BrCCC(C)C1=CC=C(C(=O)OC(C)(C)C)C=C1 YVRUDIVGJUZATC-UHFFFAOYSA-N 0.000 description 1
- CXCJIHHVQLRJKX-OUKQBFOZSA-N tert-butyl 4-[(e)-1-ethoxy-1-oxopent-2-en-3-yl]benzoate Chemical compound CCOC(=O)\C=C(/CC)C1=CC=C(C(=O)OC(C)(C)C)C=C1 CXCJIHHVQLRJKX-OUKQBFOZSA-N 0.000 description 1
- FBZWUEFBLWLXIH-DHZHZOJOSA-N tert-butyl 4-[(e)-3-ethoxy-3-oxoprop-1-enyl]benzoate Chemical compound CCOC(=O)\C=C\C1=CC=C(C(=O)OC(C)(C)C)C=C1 FBZWUEFBLWLXIH-DHZHZOJOSA-N 0.000 description 1
- OSWDDVNVEXGBTG-UHFFFAOYSA-N tert-butyl 4-[2-(2-cyano-3-methoxycyclopent-2-en-1-yl)ethyl]benzoate Chemical compound C1CC(OC)=C(C#N)C1CCC1=CC=C(C(=O)OC(C)(C)C)C=C1 OSWDDVNVEXGBTG-UHFFFAOYSA-N 0.000 description 1
- QDZHTSUAGUMODC-UHFFFAOYSA-N tert-butyl 4-[2-(2-methoxycarbonyl-3-oxocyclopentyl)ethyl]benzoate Chemical compound C1CC(=O)C(C(=O)OC)C1CCC1=CC=C(C(=O)OC(C)(C)C)C=C1 QDZHTSUAGUMODC-UHFFFAOYSA-N 0.000 description 1
- UPEYQTBFNLMZTH-UHFFFAOYSA-N tert-butyl 4-[4-(2-cyano-3-methoxycyclopent-2-en-1-yl)butan-2-yl]benzoate Chemical compound C1CC(OC)=C(C#N)C1CCC(C)C1=CC=C(C(=O)OC(C)(C)C)C=C1 UPEYQTBFNLMZTH-UHFFFAOYSA-N 0.000 description 1
- QXQXBZLXIAUIBG-UHFFFAOYSA-N tert-butyl 4-acetylbenzoate Chemical compound CC(=O)C1=CC=C(C(=O)OC(C)(C)C)C=C1 QXQXBZLXIAUIBG-UHFFFAOYSA-N 0.000 description 1
- MCHIPTCUNOHZCY-UHFFFAOYSA-N tert-butyl 4-propanoylbenzoate Chemical compound CCC(=O)C1=CC=C(C(=O)OC(C)(C)C)C=C1 MCHIPTCUNOHZCY-UHFFFAOYSA-N 0.000 description 1
- ZIYSKINEEBXXGR-VQHVLOKHSA-N tert-butyl 5-[(e)-3-ethoxy-3-oxoprop-1-enyl]thiophene-2-carboxylate Chemical compound CCOC(=O)\C=C\C1=CC=C(C(=O)OC(C)(C)C)S1 ZIYSKINEEBXXGR-VQHVLOKHSA-N 0.000 description 1
- FGQULQGHCUSSTE-UHFFFAOYSA-N tert-butyl 5-[3-(2,4-diaminopyrrolo[3,2-d]pyrimidin-5-yl)propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC(C)(C)C)=CC=C1CCCN1C2=C(N)N=C(N)N=C2C=C1 FGQULQGHCUSSTE-UHFFFAOYSA-N 0.000 description 1
- FRACPXUHUTXLCX-BELIEFIBSA-N tert-butyl N-{1-[(1S)-1-{[(1R,2S)-1-(benzylcarbamoyl)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]carbamoyl}-2-cyclopropylethyl]-2-oxopyridin-3-yl}carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CN(C1=O)[C@@H](CC2CC2)C(=O)N[C@@H](C[C@@H]3CCNC3=O)[C@H](C(=O)NCC4=CC=CC=C4)O FRACPXUHUTXLCX-BELIEFIBSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- QIQITDHWZYEEPA-UHFFFAOYSA-N thiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CS1 QIQITDHWZYEEPA-UHFFFAOYSA-N 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 235000015961 tonic Nutrition 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 229960000716 tonics Drugs 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 150000004794 vinyl magnesium halides Chemical class 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 150000007934 α,β-unsaturated carboxylic acids Chemical class 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP20925291 | 1991-08-21 | ||
JP91-209252 | 1991-08-21 | ||
JP91-251548 | 1991-09-30 | ||
JP25154891 | 1991-09-30 | ||
JP92-217670 | 1992-08-17 | ||
JP91-217670 | 1992-08-17 | ||
JP21767092A JP3144903B2 (ja) | 1991-08-21 | 1992-08-17 | 縮合ピリミジン誘導体 |
Publications (2)
Publication Number | Publication Date |
---|---|
KR930004307A KR930004307A (ko) | 1993-03-22 |
KR950011740B1 true KR950011740B1 (ko) | 1995-10-09 |
Family
ID=27328976
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1019920015043A Expired - Lifetime KR950011740B1 (ko) | 1991-08-21 | 1992-08-21 | 축합된 피리미딘 유도체 |
Country Status (9)
Country | Link |
---|---|
JP (1) | JP3144903B2 (enrdf_load_stackoverflow) |
KR (1) | KR950011740B1 (enrdf_load_stackoverflow) |
CN (1) | CN1070402A (enrdf_load_stackoverflow) |
AU (1) | AU655051B2 (enrdf_load_stackoverflow) |
CA (1) | CA2076431A1 (enrdf_load_stackoverflow) |
FI (1) | FI923697A7 (enrdf_load_stackoverflow) |
HU (1) | HUT70180A (enrdf_load_stackoverflow) |
NO (1) | NO923249L (enrdf_load_stackoverflow) |
TW (1) | TW202451B (enrdf_load_stackoverflow) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HUT70208A (en) * | 1992-09-25 | 1995-09-28 | Lilly Co Eli | Process for preparing 5-substituted pyrrolo[2,3-d]-pyrimidines |
US8252804B2 (en) | 2008-10-01 | 2012-08-28 | Duquesne University Of The Holy Spirit | Selective proton coupled folate transporter and folate receptor, and GARFTase inhibitor compounds and methods of using the same |
US20110082158A1 (en) * | 2008-10-01 | 2011-04-07 | Aleem Gangjee | Selective proton coupled folate transporter and folate receptor, and garftase and/or other folate metabolizing enzymes inhibitor compounds and methods of using the same |
CN106188060A (zh) * | 2015-04-29 | 2016-12-07 | 厦门大学 | 嘧啶并吡咯类化合物、其制备方法、药用组合物及其应用 |
CN113788834B (zh) * | 2021-09-18 | 2022-11-29 | 河南奥思恩医药科技有限公司 | 2,4-二氯-6,7-二氢-5H-吡咯并[3,4-d]嘧啶盐酸盐的制备方法 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0438261A3 (en) * | 1990-01-16 | 1992-02-26 | Takeda Chemical Industries, Ltd. | Condensed heterocyclic glutamic acid derivatives, their production and use |
-
1992
- 1992-08-17 JP JP21767092A patent/JP3144903B2/ja not_active Expired - Fee Related
- 1992-08-18 FI FI923697A patent/FI923697A7/fi not_active Application Discontinuation
- 1992-08-18 TW TW081106523A patent/TW202451B/zh active
- 1992-08-19 NO NO92923249A patent/NO923249L/no unknown
- 1992-08-19 HU HU9202699A patent/HUT70180A/hu unknown
- 1992-08-19 CA CA002076431A patent/CA2076431A1/en not_active Abandoned
- 1992-08-20 AU AU21157/92A patent/AU655051B2/en not_active Ceased
- 1992-08-21 KR KR1019920015043A patent/KR950011740B1/ko not_active Expired - Lifetime
- 1992-08-21 CN CN92109669A patent/CN1070402A/zh active Pending
Also Published As
Publication number | Publication date |
---|---|
CA2076431A1 (en) | 1993-02-22 |
TW202451B (enrdf_load_stackoverflow) | 1993-03-21 |
FI923697A0 (fi) | 1992-08-18 |
KR930004307A (ko) | 1993-03-22 |
AU2115792A (en) | 1993-02-25 |
JP3144903B2 (ja) | 2001-03-12 |
FI923697A7 (fi) | 1993-02-22 |
NO923249D0 (no) | 1992-08-19 |
JPH05186437A (ja) | 1993-07-27 |
NO923249L (no) | 1993-02-22 |
CN1070402A (zh) | 1993-03-31 |
AU655051B2 (en) | 1994-12-01 |
HUT70180A (en) | 1995-09-28 |
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