JPH0433787B2 - - Google Patents
Info
- Publication number
- JPH0433787B2 JPH0433787B2 JP60142414A JP14241485A JPH0433787B2 JP H0433787 B2 JPH0433787 B2 JP H0433787B2 JP 60142414 A JP60142414 A JP 60142414A JP 14241485 A JP14241485 A JP 14241485A JP H0433787 B2 JPH0433787 B2 JP H0433787B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- hydrogen
- alkyl
- compound
- chloro
- 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
- 150000001875 compounds Chemical class 0.000 claims description 247
- 239000001257 hydrogen Substances 0.000 claims description 164
- 229910052739 hydrogen Inorganic materials 0.000 claims description 164
- 125000000217 alkyl group Chemical group 0.000 claims description 137
- -1 R 13 Chemical compound 0.000 claims description 95
- 125000003342 alkenyl group Chemical group 0.000 claims description 90
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 87
- 239000000203 mixture Substances 0.000 claims description 87
- 125000003545 alkoxy group Chemical group 0.000 claims description 84
- 150000002431 hydrogen Chemical class 0.000 claims description 77
- 125000004432 carbon atom Chemical group C* 0.000 claims description 76
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 75
- 125000000304 alkynyl group Chemical group 0.000 claims description 72
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 68
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 66
- 229910052760 oxygen Inorganic materials 0.000 claims description 66
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 61
- 239000001301 oxygen Substances 0.000 claims description 61
- 229910052757 nitrogen Chemical group 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 53
- 239000002904 solvent Substances 0.000 claims description 51
- 238000000034 method Methods 0.000 claims description 46
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 43
- 150000003242 quaternary ammonium salts Chemical group 0.000 claims description 43
- 231100000252 nontoxic Toxicity 0.000 claims description 40
- 230000003000 nontoxic effect Effects 0.000 claims description 40
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
- 229920006395 saturated elastomer Polymers 0.000 claims description 34
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 33
- 229910052717 sulfur Inorganic materials 0.000 claims description 33
- 239000011593 sulfur Chemical group 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 150000002367 halogens Chemical class 0.000 claims description 32
- 206010047700 Vomiting Diseases 0.000 claims description 28
- 229910052799 carbon Inorganic materials 0.000 claims description 28
- 125000005842 heteroatom Chemical group 0.000 claims description 28
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 28
- 239000012453 solvate Substances 0.000 claims description 26
- 239000002111 antiemetic agent Substances 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 238000006243 chemical reaction Methods 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 19
- 230000003474 anti-emetic effect Effects 0.000 claims description 18
- 125000004429 atom Chemical group 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 16
- 150000001721 carbon Chemical group 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 14
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 14
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 239000012312 sodium hydride Substances 0.000 claims description 13
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 12
- 125000001246 bromo group Chemical group Br* 0.000 claims description 12
- 125000001153 fluoro group Chemical group F* 0.000 claims description 12
- 230000030135 gastric motility Effects 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 11
- 150000004677 hydrates Chemical class 0.000 claims description 11
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 10
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 claims description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 229960004503 metoclopramide Drugs 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 5
- ZTXYPANIEPFDPQ-UHFFFAOYSA-N 4-amino-5-chloro-2-(cyanomethoxy)-n-[2-(diethylamino)ethyl]benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OCC#N ZTXYPANIEPFDPQ-UHFFFAOYSA-N 0.000 claims description 4
- STINTIGQRLYQGY-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-(2-oxopentan-3-yloxy)benzamide Chemical compound CCC(C(C)=O)OC1=CC(N)=C(Cl)C=C1C(=O)NCCN(CC)CC STINTIGQRLYQGY-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 4
- PXWVSXGJMAKADL-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-(1,3-dioxolan-2-yloxy)benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC1OCCO1 PXWVSXGJMAKADL-UHFFFAOYSA-N 0.000 claims description 3
- XWXSUOFPQBJJNG-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-(2,2-dimethoxyethoxy)benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OCC(OC)OC XWXSUOFPQBJJNG-UHFFFAOYSA-N 0.000 claims description 3
- JYSBWWBKJZCBFN-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-(2-hydroxyethoxy)benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OCCO JYSBWWBKJZCBFN-UHFFFAOYSA-N 0.000 claims description 3
- GATCOSFCYSJURA-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-(2-hydroxypropoxy)benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OCC(C)O GATCOSFCYSJURA-UHFFFAOYSA-N 0.000 claims description 3
- ZVPMWLYIHMIYJK-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-(2-methoxyethoxymethoxy)benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OCOCCOC ZVPMWLYIHMIYJK-UHFFFAOYSA-N 0.000 claims description 3
- DDCPQGNTWWVLGM-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-(2-oxobutoxy)benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OCC(=O)CC DDCPQGNTWWVLGM-UHFFFAOYSA-N 0.000 claims description 3
- FTMLVIOQPVOHIU-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-(2-oxopentoxy)benzamide Chemical compound CCCC(=O)COC1=CC(N)=C(Cl)C=C1C(=O)NCCN(CC)CC FTMLVIOQPVOHIU-UHFFFAOYSA-N 0.000 claims description 3
- MCNMUWHWVANETD-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-(2-oxopropoxy)benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OCC(C)=O MCNMUWHWVANETD-UHFFFAOYSA-N 0.000 claims description 3
- SBQNXJKQGLWJLB-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-[2-(2-methoxyethoxy)ethoxy]benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OCCOCCOC SBQNXJKQGLWJLB-UHFFFAOYSA-N 0.000 claims description 3
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 3
- CHDLKHBVTYXBAR-UHFFFAOYSA-N 2-[2-(diethylamino)ethyl]benzamide Chemical compound CCN(CC)CCC1=CC=CC=C1C(N)=O CHDLKHBVTYXBAR-UHFFFAOYSA-N 0.000 claims description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- OMSUUTLTLCFHGV-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-(2-methoxyethoxy)benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OCCOC OMSUUTLTLCFHGV-UHFFFAOYSA-N 0.000 claims description 2
- QIIYAJZQOKYUDR-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-(2-oxocyclohexyl)oxybenzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC1C(=O)CCCC1 QIIYAJZQOKYUDR-UHFFFAOYSA-N 0.000 claims description 2
- NZOKUUUJIFFZKA-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-(oxolan-2-ylmethoxy)benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OCC1OCCC1 NZOKUUUJIFFZKA-UHFFFAOYSA-N 0.000 claims description 2
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 claims description 2
- 238000007796 conventional method Methods 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 2
- 239000012442 inert solvent Substances 0.000 claims description 2
- 150000002926 oxygen Chemical class 0.000 claims description 2
- 239000002243 precursor Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 23
- 150000002148 esters Chemical class 0.000 claims 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 11
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 2
- 230000003301 hydrolyzing effect Effects 0.000 claims 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims 2
- ZUWGURNGYMEHHU-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-(2-hydrazinyl-2-oxoethoxy)benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OCC(=O)NN ZUWGURNGYMEHHU-UHFFFAOYSA-N 0.000 claims 1
- WQDSYTGTSMCTOH-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-(2-methylsulfinylethoxy)benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OCCS(C)=O WQDSYTGTSMCTOH-UHFFFAOYSA-N 0.000 claims 1
- SCZOBUCEGRITKJ-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-(3-oxopentan-2-yloxy)benzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC(C)C(=O)CC SCZOBUCEGRITKJ-UHFFFAOYSA-N 0.000 claims 1
- HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 claims 1
- UYMKPFRHYYNDTL-UHFFFAOYSA-N ethenamine Chemical compound NC=C UYMKPFRHYYNDTL-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 228
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 144
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 77
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 72
- 238000004458 analytical method Methods 0.000 description 70
- 239000000243 solution Substances 0.000 description 58
- 239000007787 solid Substances 0.000 description 48
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 41
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 40
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
- 238000012360 testing method Methods 0.000 description 29
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 25
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 25
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 23
- 229910021529 ammonia Inorganic materials 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 239000012074 organic phase Substances 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 238000010992 reflux Methods 0.000 description 17
- 238000002360 preparation method Methods 0.000 description 16
- 229940125683 antiemetic agent Drugs 0.000 description 15
- 229910000027 potassium carbonate Inorganic materials 0.000 description 15
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 15
- 239000000377 silicon dioxide Substances 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 239000000284 extract Substances 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- HPSMMIJTHMWCGC-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-hydroxybenzamide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1O HPSMMIJTHMWCGC-UHFFFAOYSA-N 0.000 description 12
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 12
- 229960004046 apomorphine Drugs 0.000 description 12
- 150000003936 benzamides Chemical class 0.000 description 12
- 239000012267 brine Substances 0.000 description 12
- 239000000872 buffer Substances 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 12
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 239000012043 crude product Substances 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 8
- 229960000581 salicylamide Drugs 0.000 description 8
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 230000008673 vomiting Effects 0.000 description 8
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 7
- 241000282472 Canis lupus familiaris Species 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 238000002512 chemotherapy Methods 0.000 description 7
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 7
- 229960004316 cisplatin Drugs 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 7
- JXIGWAINVIWPQD-UHFFFAOYSA-N 4-amino-5-chloro-n-[2-(diethylamino)ethyl]-2-hydroxybenzamide;hydrochloride Chemical compound Cl.CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1O JXIGWAINVIWPQD-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 230000008485 antagonism Effects 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 229940054066 benzamide antipsychotics Drugs 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 5
- 235000008504 concentrate Nutrition 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 235000009518 sodium iodide Nutrition 0.000 description 5
- 229950001675 spiperone Drugs 0.000 description 5
- MYFKLQFBFSHBPA-UHFFFAOYSA-N 1-chloro-2-methylsulfanylethane Chemical compound CSCCCl MYFKLQFBFSHBPA-UHFFFAOYSA-N 0.000 description 4
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 4
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 4
- 230000003291 dopaminomimetic effect Effects 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
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- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Pyrrole Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62574284A | 1984-06-28 | 1984-06-28 | |
| US625742 | 1984-06-28 | ||
| US729513 | 1985-05-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6163642A JPS6163642A (ja) | 1986-04-01 |
| JPH0433787B2 true JPH0433787B2 (de) | 1992-06-04 |
Family
ID=24507385
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60142414A Granted JPS6163642A (ja) | 1984-06-28 | 1985-06-28 | 薬理活性置換ベンザミド |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPS6163642A (de) |
| CS (1) | CS271462B2 (de) |
| DD (1) | DD255529A5 (de) |
| SU (3) | SU1366053A3 (de) |
| ZA (1) | ZA854790B (de) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5395832A (en) * | 1991-02-15 | 1995-03-07 | Hokuriku Seiyaku Co., Ltd. | Benzamide derivatives |
| TW213460B (de) * | 1991-02-15 | 1993-09-21 | Hokuriku Pharmaceutical |
-
1985
- 1985-06-25 ZA ZA854790A patent/ZA854790B/xx unknown
- 1985-06-27 CS CS854724A patent/CS271462B2/cs unknown
- 1985-06-27 SU SU853914151A patent/SU1366053A3/ru active
- 1985-06-27 DD DD27788685A patent/DD255529A5/de not_active IP Right Cessation
- 1985-06-28 JP JP60142414A patent/JPS6163642A/ja active Granted
-
1986
- 1986-04-22 SU SU864027330A patent/SU1398771A3/ru active
-
1987
- 1987-06-08 SU SU874202671A patent/SU1517759A3/ru active
Also Published As
| Publication number | Publication date |
|---|---|
| CS472485A2 (en) | 1990-03-14 |
| CS271462B2 (en) | 1990-10-12 |
| SU1366053A3 (ru) | 1988-01-07 |
| JPS6163642A (ja) | 1986-04-01 |
| SU1398771A3 (ru) | 1988-06-15 |
| ZA854790B (en) | 1986-02-26 |
| SU1517759A3 (ru) | 1989-10-23 |
| DD255529A5 (de) | 1988-04-06 |
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