JPS62149696A

JPS62149696A - ２′−デオキシ−５−フルオロウリジン誘導体

２′−デオキシ−５−フルオロウリジン誘導体

Info

Publication number: JPS62149696A
Authority: JP; Japan
Prior art keywords: group; pyridyl; deoxy; fluorouridine; chloro
Prior art date: 1984-11-30
Legal status : Granted

Application number

JP60269172A

Other languages

English (en)

Japanese (ja)

Other versions

JPH0153878B2 (enrdf_load_stackoverflow

Inventor

Setsuo Fujii

藤井　節郎

Current Assignee

Otsuka Pharmaceutical Co Ltd

Original Assignee

Otsuka Pharmaceutical Co Ltd

Priority date

1984-11-30

Filing date

1985-11-27

Publication date

1987-07-03

1985-11-27 Application filed by Otsuka Pharmaceutical Co Ltd filed Critical Otsuka Pharmaceutical Co Ltd

1987-07-03 Publication of JPS62149696A publication Critical patent/JPS62149696A/ja

1989-11-15 Publication of JPH0153878B2 publication Critical patent/JPH0153878B2/ja

Status Granted legal-status Critical Current

Links

ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical class C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 title claims description 15
125000000217 alkyl group Chemical group 0.000 claims abstract description 80
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 57
125000002252 acyl group Chemical group 0.000 claims abstract description 42
125000001424 substituent group Chemical group 0.000 claims abstract description 35
125000005843 halogen group Chemical group 0.000 claims abstract description 26
125000003342 alkenyl group Chemical group 0.000 claims abstract description 19
125000003545 alkoxy group Chemical group 0.000 claims description 44
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 28
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
125000003277 amino group Chemical group 0.000 claims description 14
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
125000005530 alkylenedioxy group Chemical group 0.000 claims description 10
125000001624 naphthyl group Chemical group 0.000 claims description 10
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 7
239000000126 substance Substances 0.000 claims 1
-1 tetrahydrophenyl Chemical group 0.000 abstract description 768
150000001875 compounds Chemical class 0.000 abstract description 210
239000002904 solvent Substances 0.000 abstract description 53
238000002360 preparation method Methods 0.000 abstract description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract description 15
239000003795 chemical substances by application Substances 0.000 abstract description 6
238000006704 dehydrohalogenation reaction Methods 0.000 abstract description 4
239000002246 antineoplastic agent Substances 0.000 abstract description 3
229910052736 halogen Inorganic materials 0.000 abstract description 3
238000005947 deacylation reaction Methods 0.000 abstract description 2
150000002367 halogens Chemical class 0.000 abstract description 2
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 2
GAYMOAUALRXKAU-BFHYXJOUSA-N 5-fluoro-1-[(2r,4s,5r)-4-hydroxy-5-(phenylmethoxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound C([C@H]1O[C@H](C[C@@H]1O)N1C(NC(=O)C(F)=C1)=O)OCC1=CC=CC=C1 GAYMOAUALRXKAU-BFHYXJOUSA-N 0.000 abstract 1
230000003327 cancerostatic effect Effects 0.000 abstract 1
239000007795 chemical reaction product Substances 0.000 abstract 1
238000010511 deprotection reaction Methods 0.000 abstract 1
231100000053 low toxicity Toxicity 0.000 abstract 1
239000000463 material Substances 0.000 abstract 1
238000006243 chemical reaction Methods 0.000 description 169
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 142
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 126
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 93
238000004519 manufacturing process Methods 0.000 description 71
238000002844 melting Methods 0.000 description 69
230000008018 melting Effects 0.000 description 69
238000005160 1H NMR spectroscopy Methods 0.000 description 61
239000000243 solution Substances 0.000 description 61
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 58
239000000843 powder Substances 0.000 description 54
239000000203 mixture Substances 0.000 description 53
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 53
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 48
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 41
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 description 39
125000004432 carbon atom Chemical group C* 0.000 description 34
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 33
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
238000005481 NMR spectroscopy Methods 0.000 description 30
DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 29
238000000034 method Methods 0.000 description 29
239000003921 oil Substances 0.000 description 26
235000019198 oils Nutrition 0.000 description 26
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 21
229910052739 hydrogen Inorganic materials 0.000 description 21
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
239000010410 layer Substances 0.000 description 20
239000000741 silica gel Substances 0.000 description 20
229910002027 silica gel Inorganic materials 0.000 description 20
235000019441 ethanol Nutrition 0.000 description 19
FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical group O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 description 18
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
125000002887 hydroxy group Chemical group [H]O* 0.000 description 18
125000006239 protecting group Chemical group 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
239000002253 acid Substances 0.000 description 17
238000010898 silica gel chromatography Methods 0.000 description 17
235000011054 acetic acid Nutrition 0.000 description 16
125000005115 alkyl carbamoyl group Chemical group 0.000 description 16
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 16
229940045145 uridine Drugs 0.000 description 16
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 15
238000000921 elemental analysis Methods 0.000 description 15
DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 15
150000004820 halides Chemical class 0.000 description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 12
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 12
150000008065 acid anhydrides Chemical class 0.000 description 10
238000005917 acylation reaction Methods 0.000 description 10
125000003118 aryl group Chemical group 0.000 description 10
239000003826 tablet Substances 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
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 9
239000000460 chlorine Substances 0.000 description 9
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 9
230000002829 reductive effect Effects 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
125000004423 acyloxy group Chemical group 0.000 description 8
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
238000009472 formulation Methods 0.000 description 8
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 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
239000002994 raw material Substances 0.000 description 8
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 8
ZEZJPIDPVXJEME-UHFFFAOYSA-N 2,4-Dihydroxypyridine Chemical compound OC=1C=CNC(=O)C=1 ZEZJPIDPVXJEME-UHFFFAOYSA-N 0.000 description 7
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 7
229920002472 Starch Polymers 0.000 description 7
FDQSRULYDNDXQB-UHFFFAOYSA-N benzene-1,3-dicarbonyl chloride Chemical compound ClC(=O)C1=CC=CC(C(Cl)=O)=C1 FDQSRULYDNDXQB-UHFFFAOYSA-N 0.000 description 7
239000002775 capsule Substances 0.000 description 7
229910052799 carbon Inorganic materials 0.000 description 7
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 7
239000013078 crystal Substances 0.000 description 7
239000012442 inert solvent Substances 0.000 description 7
239000008101 lactose Substances 0.000 description 7
DCMUJUQQBAFVLJ-UHFFFAOYSA-N oxolan-2-yl acetate Chemical compound CC(=O)OC1CCCO1 DCMUJUQQBAFVLJ-UHFFFAOYSA-N 0.000 description 7
239000008107 starch Substances 0.000 description 7
235000019698 starch Nutrition 0.000 description 7
239000000725 suspension Substances 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
206010028980 Neoplasm Diseases 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
229910021627 Tin(IV) chloride Inorganic materials 0.000 description 6
150000001350 alkyl halides Chemical class 0.000 description 6
150000004945 aromatic hydrocarbons Chemical class 0.000 description 6
150000007514 bases Chemical class 0.000 description 6
229910052792 caesium Inorganic materials 0.000 description 6
229910002091 carbon monoxide Inorganic materials 0.000 description 6
239000001913 cellulose Substances 0.000 description 6
229920002678 cellulose Polymers 0.000 description 6
125000004093 cyano group Chemical group *C#N 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 6
MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical group C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 5
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
125000000304 alkynyl group Chemical group 0.000 description 5
125000000732 arylene group Chemical group 0.000 description 5
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
238000001816 cooling Methods 0.000 description 5
238000003379 elimination reaction Methods 0.000 description 5
125000000524 functional group Chemical group 0.000 description 5
239000008103 glucose Substances 0.000 description 5
LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 5
239000000825 pharmaceutical preparation Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
WKNFSOJIZMYCBM-UHFFFAOYSA-N (5-chloro-2-oxo-1h-pyridin-4-yl) acetate Chemical group CC(=O)OC1=CC(=O)NC=C1Cl WKNFSOJIZMYCBM-UHFFFAOYSA-N 0.000 description 4
SLRRHYHVZYNBTK-UHFFFAOYSA-N (5-chloro-2-oxo-1h-pyridin-4-yl) benzoate Chemical group ClC1=CNC(=O)C=C1OC(=O)C1=CC=CC=C1 SLRRHYHVZYNBTK-UHFFFAOYSA-N 0.000 description 4
125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 4
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
239000002841 Lewis acid Substances 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
150000001266 acyl halides Chemical class 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 4
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
239000000969 carrier Substances 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 4
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
239000003814 drug Substances 0.000 description 4
239000000839 emulsion Substances 0.000 description 4
150000002170 ethers Chemical class 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
239000008187 granular material Substances 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000002198 insoluble material Substances 0.000 description 4
150000007517 lewis acids Chemical class 0.000 description 4
239000007788 liquid Substances 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
238000002156 mixing Methods 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
125000004433 nitrogen atom Chemical group N* 0.000 description 4
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 4
125000005633 phthalidyl group Chemical group 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
150000003222 pyridines Chemical class 0.000 description 4
229910052717 sulfur Inorganic materials 0.000 description 4
239000011592 zinc chloride Substances 0.000 description 4
235000005074 zinc chloride Nutrition 0.000 description 4
MFRXQJIPCLKQML-UHFFFAOYSA-N (5-chloro-4-oxo-1h-pyridin-2-yl) benzoate Chemical compound C1=C(Cl)C(O)=CC(OC(=O)C=2C=CC=CC=2)=N1 MFRXQJIPCLKQML-UHFFFAOYSA-N 0.000 description 3
WGVYCXYGPNNUQA-UHFFFAOYSA-N 1-(bromomethyl)-2-methylbenzene Chemical compound CC1=CC=CC=C1CBr WGVYCXYGPNNUQA-UHFFFAOYSA-N 0.000 description 3
WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 3
125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
125000006279 3-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Br)=C1[H])C([H])([H])* 0.000 description 3
125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 description 3
125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 3
UWDMKTDPDJCJOP-UHFFFAOYSA-N 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-ium-4-carboxylate Chemical compound CC1(C)CC(O)(C(O)=O)CC(C)(C)N1 UWDMKTDPDJCJOP-UHFFFAOYSA-N 0.000 description 3
125000006491 4-t-butyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
239000005995 Aluminium silicate Substances 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
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