CA1125759A - Procede d'obtention de nouveaux composes amido a base d'uree - Google Patents

Procede d'obtention de nouveaux composes amido a base d'uree

Info

Publication number: CA1125759A
Authority: CA; Canada
Prior art keywords: pyridyl; ethyl; urea; phenyl; formula
Prior art date: 1979-02-15
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

Application number

CA321,545A

Other languages

English (en)

Inventor

Adrian Marxer

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Novartis AG

Original Assignee

Ciba Geigy Investments Ltd

Priority date (The priority date 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 date listed.)

1979-02-15

Filing date

1979-02-15

Publication date

1982-06-15

1979-02-15 Application filed by Ciba Geigy Investments Ltd filed Critical Ciba Geigy Investments Ltd

1979-02-15 Priority to CA321,545A priority Critical patent/CA1125759A/fr

1979-08-08 Priority to IE591/79A priority patent/IE47864B1/en

1982-06-15 Application granted granted Critical

1982-06-15 Publication of CA1125759A publication Critical patent/CA1125759A/fr

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 35
239000004202 carbamide Substances 0.000 title claims abstract description 32
238000002360 preparation method Methods 0.000 title claims abstract description 9
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title abstract description 9
125000003368 amide group Chemical group 0.000 title abstract description 3
150000001875 compounds Chemical class 0.000 claims abstract description 56
125000001841 imino group Chemical group [H]N=* 0.000 claims abstract description 12
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 11
229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
239000001301 oxygen Substances 0.000 claims abstract description 11
125000004076 pyridyl group Chemical group 0.000 claims abstract description 8
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 5
229910052717 sulfur Chemical group 0.000 claims abstract description 5
239000011593 sulfur Chemical group 0.000 claims abstract description 5
150000003839 salts Chemical class 0.000 claims description 56
239000000203 mixture Substances 0.000 claims description 26
239000002253 acid Substances 0.000 claims description 20
RPNUMPOLZDHAAY-UHFFFAOYSA-N Diethylenetriamine Chemical class NCCNCCN RPNUMPOLZDHAAY-UHFFFAOYSA-N 0.000 claims description 17
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
MGYGFNQQGAQEON-UHFFFAOYSA-N 4-tolyl isocyanate Chemical compound CC1=CC=C(N=C=O)C=C1 MGYGFNQQGAQEON-UHFFFAOYSA-N 0.000 claims description 13
239000000126 substance Substances 0.000 claims description 12
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 11
CFEPCPHKICBCJV-UHFFFAOYSA-N ethyl 4-isocyanatobenzoate Chemical compound CCOC(=O)C1=CC=C(N=C=O)C=C1 CFEPCPHKICBCJV-UHFFFAOYSA-N 0.000 claims description 9
229910052740 iodine Inorganic materials 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 7
230000003287 optical effect Effects 0.000 claims description 7
125000000217 alkyl group Chemical group 0.000 claims description 6
150000008064 anhydrides Chemical class 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
239000000460 chlorine Substances 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
150000004820 halides Chemical class 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
MVHAVEMWHWQFRP-UHFFFAOYSA-N 1-[2-[2-(2-chlorophenyl)-4,5-dihydroimidazol-1-yl]ethyl]-3-(4-methylphenyl)urea Chemical compound C1=CC(C)=CC=C1NC(=O)NCCN1C(C=2C(=CC=CC=2)Cl)=NCC1 MVHAVEMWHWQFRP-UHFFFAOYSA-N 0.000 claims description 3
KDMDSIUVFBXDDB-UHFFFAOYSA-N 4-[2-(2-pyridin-2-yl-4,5-dihydroimidazol-1-yl)ethylcarbamoylamino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC(=O)NCCN1C(C=2N=CC=CC=2)=NCC1 KDMDSIUVFBXDDB-UHFFFAOYSA-N 0.000 claims description 3
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
CLMYYDPLOSKEHT-UHFFFAOYSA-N ethyl 4-[2-(2-pyridin-2-yl-4,5-dihydroimidazol-1-yl)ethylcarbamoylamino]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1NC(=O)NCCN1C(C=2N=CC=CC=2)=NCC1 CLMYYDPLOSKEHT-UHFFFAOYSA-N 0.000 claims description 3
QBVPWMWOTZZZRZ-UHFFFAOYSA-N 4-[2-(2-pyridin-4-yl-4,5-dihydroimidazol-1-yl)ethylcarbamoylamino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC(=O)NCCN1C(C=2C=CN=CC=2)=NCC1 QBVPWMWOTZZZRZ-UHFFFAOYSA-N 0.000 claims description 2
GNVMUORYQLCPJZ-UHFFFAOYSA-N carbamothioic s-acid Chemical compound NC(S)=O GNVMUORYQLCPJZ-UHFFFAOYSA-N 0.000 claims description 2
OVTCTNXNXDEZRG-UHFFFAOYSA-N ethyl 4-[2-(2-pyridin-4-yl-4,5-dihydroimidazol-1-yl)ethylcarbamoylamino]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1NC(=O)NCCN1C(C=2C=CN=CC=2)=NCC1 OVTCTNXNXDEZRG-UHFFFAOYSA-N 0.000 claims description 2
KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 8
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 claims 5
230000003301 hydrolyzing effect Effects 0.000 claims 2
206010028980 Neoplasm Diseases 0.000 abstract description 3
239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 87
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 57
239000000243 solution Substances 0.000 description 45
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
239000000155 melt Substances 0.000 description 33
238000002844 melting Methods 0.000 description 26
230000008018 melting Effects 0.000 description 26
238000006243 chemical reaction Methods 0.000 description 25
235000019439 ethyl acetate Nutrition 0.000 description 24
229940093499 ethyl acetate Drugs 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
239000002585 base Substances 0.000 description 19
235000011167 hydrochloric acid Nutrition 0.000 description 19
229960000443 hydrochloric acid Drugs 0.000 description 19
230000001476 alcoholic effect Effects 0.000 description 18
238000000354 decomposition reaction Methods 0.000 description 18
239000004480 active ingredient Substances 0.000 description 16
239000007858 starting material Substances 0.000 description 16
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
229940073584 methylene chloride Drugs 0.000 description 11
239000000047 product Substances 0.000 description 11
235000011121 sodium hydroxide Nutrition 0.000 description 11
229940083608 sodium hydroxide Drugs 0.000 description 11
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 10
-1 methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy Chemical group 0.000 description 10
239000002904 solvent Substances 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
239000013078 crystal Substances 0.000 description 9
238000002425 crystallisation Methods 0.000 description 9
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 9
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 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
239000002244 precipitate Substances 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
108010010803 Gelatin Proteins 0.000 description 7
238000009835 boiling Methods 0.000 description 7
239000008273 gelatin Substances 0.000 description 7
229940014259 gelatin Drugs 0.000 description 7
229920000159 gelatin Polymers 0.000 description 7
235000019322 gelatine Nutrition 0.000 description 7
235000011852 gelatine desserts Nutrition 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
239000008298 dragée Substances 0.000 description 6
229960004592 isopropanol Drugs 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
239000007940 sugar coated tablet Substances 0.000 description 6
TVOGFKKPKAUXME-UHFFFAOYSA-N 1-[2-(2-chlorophenyl)-4,5-dihydroimidazol-1-yl]ethanamine Chemical compound CC(N)N1CCN=C1C1=CC=CC=C1Cl TVOGFKKPKAUXME-UHFFFAOYSA-N 0.000 description 5
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 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 5
239000002775 capsule Substances 0.000 description 5
238000001035 drying Methods 0.000 description 5
235000019441 ethanol Nutrition 0.000 description 5
239000007789 gas Substances 0.000 description 5
239000008101 lactose Substances 0.000 description 5
229920001592 potato starch Polymers 0.000 description 5
239000007787 solid Substances 0.000 description 5
239000003826 tablet Substances 0.000 description 5
239000000454 talc Substances 0.000 description 5
229910052623 talc Inorganic materials 0.000 description 5
RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
229930006000 Sucrose Natural products 0.000 description 4
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
229910021529 ammonia Inorganic materials 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000008187 granular material Substances 0.000 description 4
229910000037 hydrogen sulfide Inorganic materials 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
229940057948 magnesium stearate Drugs 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
239000005720 sucrose Substances 0.000 description 4
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FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
229960000583 acetic acid Drugs 0.000 description 3
239000012670 alkaline solution Substances 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
239000000969 carrier Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000008119 colloidal silica Substances 0.000 description 3
239000008120 corn starch Substances 0.000 description 3
238000001914 filtration Methods 0.000 description 3
239000012458 free base Substances 0.000 description 3
150000002367 halogens Chemical class 0.000 description 3
125000001072 heteroaryl group Chemical group 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
229940068917 polyethylene glycols Drugs 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
238000000746 purification Methods 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
235000010356 sorbitol Nutrition 0.000 description 3
229960002920 sorbitol Drugs 0.000 description 3
239000000725 suspension Substances 0.000 description 3
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 3
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
UEZHWSJXINJBRE-UHFFFAOYSA-N 1-(2-pyridin-4-yl-4,5-dihydroimidazol-1-yl)ethanamine Chemical compound CC(N)N1CCN=C1C1=CC=NC=C1 UEZHWSJXINJBRE-UHFFFAOYSA-N 0.000 description 2
SXJYSIBLFGQAND-UHFFFAOYSA-N 1-isocyanato-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(N=C=O)=C1 SXJYSIBLFGQAND-UHFFFAOYSA-N 0.000 description 2
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
NHWQMJMIYICNBP-UHFFFAOYSA-N 2-chlorobenzonitrile Chemical compound ClC1=CC=CC=C1C#N NHWQMJMIYICNBP-UHFFFAOYSA-N 0.000 description 2
JYNVJWXDTVITNH-UHFFFAOYSA-N 3-(2-pyridin-4-yl-5,6-dihydro-4h-pyrimidin-1-yl)propan-1-amine Chemical compound NCCCN1CCCN=C1C1=CC=NC=C1 JYNVJWXDTVITNH-UHFFFAOYSA-N 0.000 description 2
244000215068 Acacia senegal Species 0.000 description 2
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 2
229920000945 Amylopectin Polymers 0.000 description 2
206010003445 Ascites Diseases 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
229920000084 Gum arabic Polymers 0.000 description 2
241000699673 Mesocricetus auratus Species 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
229920001800 Shellac Polymers 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
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235000010489 acacia gum Nutrition 0.000 description 2
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
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239000003795 chemical substances by application Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000006482 condensation reaction Methods 0.000 description 2
238000001816 cooling Methods 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
238000004821 distillation Methods 0.000 description 2
239000012153 distilled water Substances 0.000 description 2
239000000975 dye Substances 0.000 description 2
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239000012362 glacial acetic acid Substances 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
239000012948 isocyanate Substances 0.000 description 2
150000002513 isocyanates Chemical class 0.000 description 2
GKQPCPXONLDCMU-CCEZHUSRSA-N lacidipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C1=CC=CC=C1\C=C\C(=O)OC(C)(C)C GKQPCPXONLDCMU-CCEZHUSRSA-N 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
210000000867 larynx Anatomy 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
239000011976 maleic acid Substances 0.000 description 2
239000001630 malic acid Substances 0.000 description 2
235000011090 malic acid Nutrition 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
GHMVPHJIZJLNHO-UHFFFAOYSA-N n-[[1-(1-aminoethyl)-4,5-dihydroimidazol-2-yl]methyl]-2-chloroaniline Chemical compound CC(N)N1CCN=C1CNC1=CC=CC=C1Cl GHMVPHJIZJLNHO-UHFFFAOYSA-N 0.000 description 2
HVFSJXUIRWUHRG-UHFFFAOYSA-N oic acid Natural products C1CC2C3CC=C4CC(OC5C(C(O)C(O)C(CO)O5)O)CC(O)C4(C)C3CCC2(C)C1C(C)C(O)CC(C)=C(C)C(=O)OC1OC(COC(C)=O)C(O)C(O)C1OC(C(C1O)O)OC(COC(C)=O)C1OC1OC(CO)C(O)C(O)C1O HVFSJXUIRWUHRG-UHFFFAOYSA-N 0.000 description 2
239000012188 paraffin wax Substances 0.000 description 2
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125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
150000002540 isothiocyanates Chemical class 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
229930182817 methionine Natural products 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 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
244000005700 microbiome Species 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
VRXQDECQRZYNJZ-UHFFFAOYSA-N n-[[1-(1-aminoethyl)-4,5-dihydroimidazol-2-yl]methyl]-2,6-dichloroaniline Chemical compound CC(N)N1CCN=C1CNC1=C(Cl)C=CC=C1Cl VRXQDECQRZYNJZ-UHFFFAOYSA-N 0.000 description 1
NOWLBFMSDPRQFL-UHFFFAOYSA-N n-[[1-(1-aminoethyl)-4,5-dihydroimidazol-2-yl]methyl]-4-chloroaniline Chemical compound CC(N)N1CCN=C1CNC1=CC=C(Cl)C=C1 NOWLBFMSDPRQFL-UHFFFAOYSA-N 0.000 description 1
XMYSHSUOSFMIBT-UHFFFAOYSA-N n-[[1-(1-aminoethyl)-4,5-dihydroimidazol-2-yl]methyl]aniline Chemical compound CC(N)N1CCN=C1CNC1=CC=CC=C1 XMYSHSUOSFMIBT-UHFFFAOYSA-N 0.000 description 1
COQOHBIAUTUPPU-UHFFFAOYSA-N n-[[1-(aminomethyl)-4,5-dihydroimidazol-2-yl]methyl]aniline Chemical compound NCN1CCN=C1CNC1=CC=CC=C1 COQOHBIAUTUPPU-UHFFFAOYSA-N 0.000 description 1
125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
125000003935 n-pentoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
231100000957 no side effect Toxicity 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 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
238000007911 parenteral administration Methods 0.000 description 1
125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
230000036647 reaction Effects 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
238000005245 sintering Methods 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
229960004799 tryptophan Drugs 0.000 description 1
235000017103 tryptophane Nutrition 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
NLVXSWCKKBEXTG-UHFFFAOYSA-N vinylsulfonic acid Chemical compound OS(=O)(=O)C=C NLVXSWCKKBEXTG-UHFFFAOYSA-N 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA321,545A 1978-03-08 1979-02-15 Procede d'obtention de nouveaux composes amido a base d'uree Expired CA1125759A (fr)

Priority Applications (2)

Application Number	Priority Date	Filing Date	Title
CA321,545A CA1125759A (fr)	1979-02-15	1979-02-15	Procede d'obtention de nouveaux composes amido a base d'uree
IE591/79A IE47864B1 (en)	1978-03-08	1979-08-08	Process for the preparation of novel urea and amido compounds

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA321,545A CA1125759A (fr)	1979-02-15	1979-02-15	Procede d'obtention de nouveaux composes amido a base d'uree

Publications (1)

Publication Number	Publication Date
CA1125759A true CA1125759A (fr)	1982-06-15

Family

ID=4113547

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA321,545A Expired CA1125759A (fr)	1978-03-08	1979-02-15	Procede d'obtention de nouveaux composes amido a base d'uree

Country Status (1)

Country	Link
CA (1)	CA1125759A (fr)

1979
- 1979-02-15 CA CA321,545A patent/CA1125759A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1999-06-15	MKEX	Expiry

Publication	Publication Date	Title
EP0008203B1 (fr)	1982-08-25	Dérivés de la thiazolidine, leur préparation et compositions pharmaceutiques les contenant
US4367335A (en)	1983-01-04	Thiazolidinylalkylene piperazine derivatives
CS207791B2 (en)	1981-08-31	Method of making the derivatives of the thiadiazole
US4420619A (en)	1983-12-13	Imidazole urea and amido compounds
FI63573C (fi)	1985-05-15	Foerfarande foer framstaellning av oxibensotiazin-dioxiders kaboxamider
US4305944A (en)	1981-12-15	N-[(4-[3-cyano substituted pyridyl]piperazino)alkyl]-azaspirodecanediones
EP0006614A2 (fr)	1980-01-09	Pyridyl- et imidazopyridyloxypropanolamines, leur procédé de préparation et compositions pharmaceutiques les contenant
JPS62252780A (ja)	1987-11-04	新規なインデノチアゾ−ル誘導体及びその製造法
EP0598123A1 (fr)	1994-05-25	Derive de piperazine et medicament contenant ce derive
EP0120558A1 (fr)	1984-10-03	Pipérazino-N-alcanoylanilides antihypertensives
KR870000912B1 (ko)	1987-05-06	디하이드로피리딘 유도체의 제조방법
CA1125759A (fr)	1982-06-15	Procede d'obtention de nouveaux composes amido a base d'uree
US4935424A (en)	1990-06-19	4 or 5-(substituted piperazinylalkyl)-2-aminothiazoles as antipsychotic agents
EP0117345B1 (fr)	1990-02-28	Aminopyrimidinones utiles comme antagonistes d'histamine H2
JPS58128384A (ja)	1983-07-30	ベンゾジオキシン化合物、その製造方法、および精神作用障害治療用医薬組成物
JPS6330903B2 (fr)	1988-06-21
EP0009362B1 (fr)	1984-06-27	Dérivés hétérocycliques de guanidine, procédé pour leur préparation et compositions pharmaceutiques les contenant
KR840002310B1 (ko)	1984-12-17	구아니딘 화합물의 제조방법
IE47864B1 (en)	1984-07-11	Process for the preparation of novel urea and amido compounds
EP0159012A2 (fr)	1985-10-23	Sulfonamidines, procédé pour leur préparation et compositions pharmaceutiques les contenant
JP2962176B2 (ja)	1999-10-12	２−［４−（置換アミジノ）ベンゾイルイミノ］チアゾリン誘導体
EP0393109B1 (fr)	1994-03-23	Nouveaux derives de 2,3-thiomorpholinedione-2-oxime, compositions pharmaceutiques contenant ces derives et procede servant a leur preparation
CA1125286A (fr)	1982-06-08	Procede de preparation de nouvelles piperazines disubstituees
US4224331A (en)	1980-09-23	Derivatives of 2-pyridylthiourea and pharmaceutical compositions
KR850000766B1 (ko)	1985-05-29	티아졸린 유도체의 제조방법