CA1142183A - Derives de nitrosouree, compositions pharmaceutiques a base de ces derives et methode de preparation - Google Patents
Derives de nitrosouree, compositions pharmaceutiques a base de ces derives et methode de preparationInfo
- Publication number
- CA1142183A CA1142183A CA000361277A CA361277A CA1142183A CA 1142183 A CA1142183 A CA 1142183A CA 000361277 A CA000361277 A CA 000361277A CA 361277 A CA361277 A CA 361277A CA 1142183 A CA1142183 A CA 1142183A
- Authority
- CA
- Canada
- Prior art keywords
- group
- carbon atoms
- pharmaceutically
- acid addition
- chloroethyl
- 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
Links
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical class NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 title claims description 18
- 238000002360 preparation method Methods 0.000 title claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 239000002253 acid Substances 0.000 claims abstract description 34
- 150000003839 salts Chemical class 0.000 claims abstract description 34
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 18
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 4
- 125000001424 substituent group Chemical group 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims description 7
- HVRKBMKIFXIHBP-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[5-(dimethylamino)-4-methyl-2,2-diphenylpentyl]-1-nitrosourea Chemical compound C=1C=CC=CC=1C(CNC(=O)N(CCCl)N=O)(CC(CN(C)C)C)C1=CC=CC=C1 HVRKBMKIFXIHBP-UHFFFAOYSA-N 0.000 claims description 4
- -1 cyano, phenyl Chemical group 0.000 claims description 4
- 239000012458 free base Substances 0.000 claims description 4
- UMCVDMBHTRZCHS-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[5-(dimethylamino)-2,2-bis(4-fluorophenyl)-4-methylpentyl]-1-nitrosourea Chemical compound C=1C=C(F)C=CC=1C(CNC(=O)N(CCCl)N=O)(CC(CN(C)C)C)C1=CC=C(F)C=C1 UMCVDMBHTRZCHS-UHFFFAOYSA-N 0.000 claims description 3
- MPWUFXVBYDZWBS-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[5-(dimethylamino)-2,2-diphenylpentyl]-1-nitrosourea Chemical compound C=1C=CC=CC=1C(CNC(=O)N(CCCl)N=O)(CCCN(C)C)C1=CC=CC=C1 MPWUFXVBYDZWBS-UHFFFAOYSA-N 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 4
- 239000001257 hydrogen Substances 0.000 claims 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- 229910052731 fluorine Chemical group 0.000 claims 2
- 239000011737 fluorine Chemical group 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 241001465754 Metazoa Species 0.000 abstract description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 abstract description 6
- 150000007513 acids Chemical class 0.000 abstract description 4
- 238000002474 experimental method Methods 0.000 abstract description 4
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 4
- 125000004103 aminoalkyl group Chemical group 0.000 abstract description 2
- 230000000118 anti-neoplastic effect Effects 0.000 abstract description 2
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 2
- 125000005843 halogen group Chemical group 0.000 abstract description 2
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- 239000000243 solution Substances 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 11
- 206010028980 Neoplasm Diseases 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 9
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
- 231100000252 nontoxic Toxicity 0.000 description 8
- 230000003000 nontoxic effect Effects 0.000 description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 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
- 239000002585 base Substances 0.000 description 4
- 239000004202 carbamide Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 231100000816 toxic dose Toxicity 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000000824 cytostatic agent Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 208000003747 lymphoid leukemia Diseases 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
- 229960000819 sodium nitrite Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 102100021906 Cyclin-O Human genes 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- 101000897441 Homo sapiens Cyclin-O Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 201000010897 colon adenocarcinoma Diseases 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000011287 therapeutic dose Methods 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- OQJHYNTWRFEERK-BTJKTKAUSA-N (z)-but-2-enedioic acid;1-(2-chloroethyl)-3-[2,2-dicyclohexyl-5-(dimethylamino)pentyl]-1-nitrosourea Chemical compound OC(=O)\C=C/C(O)=O.C1CCCCC1C(CNC(=O)N(CCCl)N=O)(CCCN(C)C)C1CCCCC1 OQJHYNTWRFEERK-BTJKTKAUSA-N 0.000 description 1
- LCVJDVANMQDUGH-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[4-(dimethylamino)-2,2-bis(4-methylphenyl)butyl]-1-nitrosourea Chemical compound C=1C=C(C)C=CC=1C(CNC(=O)N(CCCl)N=O)(CCN(C)C)C1=CC=C(C)C=C1 LCVJDVANMQDUGH-UHFFFAOYSA-N 0.000 description 1
- CMXFIIWASCFHTO-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[5-(dimethylamino)-2,2-bis(1-fluorocyclohexa-2,4-dien-1-yl)pentyl]-1-nitrosourea;hydrochloride Chemical compound Cl.C1C=CC=CC1(F)C(CNC(=O)N(CCCl)N=O)(CCCN(C)C)C1(F)CC=CC=C1 CMXFIIWASCFHTO-UHFFFAOYSA-N 0.000 description 1
- BOFHONLBJUWPIC-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[5-(dimethylamino)-2,2-bis(4-fluorophenyl)-4-methylpentyl]urea Chemical compound C=1C=C(F)C=CC=1C(CNC(=O)NCCCl)(CC(CN(C)C)C)C1=CC=C(F)C=C1 BOFHONLBJUWPIC-UHFFFAOYSA-N 0.000 description 1
- YXERUDITAZTWMU-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[5-(dimethylamino)-2,2-bis(4-fluorophenyl)pentyl]-1-nitrosourea Chemical compound C=1C=C(F)C=CC=1C(CNC(=O)N(CCCl)N=O)(CCCN(C)C)C1=CC=C(F)C=C1 YXERUDITAZTWMU-UHFFFAOYSA-N 0.000 description 1
- MPRFRSIZSXEMFC-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[5-(dimethylamino)-2,2-bis(4-fluorophenyl)pentyl]urea Chemical compound C=1C=C(F)C=CC=1C(CNC(=O)NCCCl)(CCCN(C)C)C1=CC=C(F)C=C1 MPRFRSIZSXEMFC-UHFFFAOYSA-N 0.000 description 1
- ROBLJVIHYAFKDE-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[5-(dimethylamino)-2,2-bis(4-methoxyphenyl)pentyl]-1-nitrosourea Chemical compound C1=CC(OC)=CC=C1C(CCCN(C)C)(CNC(=O)N(CCCl)N=O)C1=CC=C(OC)C=C1 ROBLJVIHYAFKDE-UHFFFAOYSA-N 0.000 description 1
- FYFYVQMSIQJRPB-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[5-(dimethylamino)-2,2-diphenylpentyl]urea Chemical compound C=1C=CC=CC=1C(CNC(=O)NCCCl)(CCCN(C)C)C1=CC=CC=C1 FYFYVQMSIQJRPB-UHFFFAOYSA-N 0.000 description 1
- XLNYRJYLWRHOGU-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[5-(dimethylamino)-4-methyl-2,2-diphenylpentyl]urea Chemical compound C=1C=CC=CC=1C(CNC(=O)NCCCl)(CC(CN(C)C)C)C1=CC=CC=C1 XLNYRJYLWRHOGU-UHFFFAOYSA-N 0.000 description 1
- VDKCMIRIKKCTBB-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[5-(dipropylamino)-2,2-bis(4-fluorophenyl)pentyl]-1-nitrosourea Chemical compound C=1C=C(F)C=CC=1C(CNC(=O)N(CCCl)N=O)(CCCN(CCC)CCC)C1=CC=C(F)C=C1 VDKCMIRIKKCTBB-UHFFFAOYSA-N 0.000 description 1
- XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 description 1
- BCMYXYHEMGPZJN-UHFFFAOYSA-N 1-chloro-2-isocyanatoethane Chemical compound ClCCN=C=O BCMYXYHEMGPZJN-UHFFFAOYSA-N 0.000 description 1
- GFCKUPZCLBELGQ-UHFFFAOYSA-N 2,2-bis(4-fluorophenyl)-N',N'-dimethylpentane-1,5-diamine Chemical compound C=1C=C(F)C=CC=1C(CN)(CCCN(C)C)C1=CC=C(F)C=C1 GFCKUPZCLBELGQ-UHFFFAOYSA-N 0.000 description 1
- OBYUGVDXOGTLBI-UHFFFAOYSA-N 2,2-bis(4-fluorophenyl)-n',n',4-trimethylpentane-1,5-diamine Chemical compound C=1C=C(F)C=CC=1C(CN)(CC(CN(C)C)C)C1=CC=C(F)C=C1 OBYUGVDXOGTLBI-UHFFFAOYSA-N 0.000 description 1
- JPKIYKWSYBYKIS-UHFFFAOYSA-N 2,2-bis(4-fluorophenyl)acetonitrile Chemical compound C1=CC(F)=CC=C1C(C#N)C1=CC=C(F)C=C1 JPKIYKWSYBYKIS-UHFFFAOYSA-N 0.000 description 1
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- UGXACBBAXFABGT-UHFFFAOYSA-N 3-chloro-n,n,2-trimethylpropan-1-amine Chemical compound ClCC(C)CN(C)C UGXACBBAXFABGT-UHFFFAOYSA-N 0.000 description 1
- NYYRRBOMNHUCLB-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCCl NYYRRBOMNHUCLB-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- PCARMCDKRKRJRO-UHFFFAOYSA-N 5-(dimethylamino)-2,2-bis(4-fluorophenyl)-4-methylpentanenitrile Chemical compound C=1C=C(F)C=CC=1C(C#N)(CC(CN(C)C)C)C1=CC=C(F)C=C1 PCARMCDKRKRJRO-UHFFFAOYSA-N 0.000 description 1
- OLVIHVABJAXFMN-UHFFFAOYSA-N 5-(dimethylamino)-2,2-bis(4-fluorophenyl)pentanenitrile Chemical compound C=1C=C(F)C=CC=1C(C#N)(CCCN(C)C)C1=CC=C(F)C=C1 OLVIHVABJAXFMN-UHFFFAOYSA-N 0.000 description 1
- SKTFQHRVFFOHTQ-UHFFFAOYSA-N 8-bromo-1,3-dimethyl-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC(Br)=N2 SKTFQHRVFFOHTQ-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
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- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
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- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 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 1
- 208000006552 Lewis Lung Carcinoma Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241001676573 Minium Species 0.000 description 1
- 229910018954 NaNH2 Inorganic materials 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
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- ZFXYFBGIUFBOJW-UHFFFAOYSA-N Theophylline Natural products O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 1
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- 239000004480 active ingredient Substances 0.000 description 1
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- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 1
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- 230000001085 cytostatic effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
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- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- XIGXDAPEMVTABC-UHFFFAOYSA-N n',n',4-trimethyl-2,2-diphenylpentane-1,5-diamine Chemical compound C=1C=CC=CC=1C(CN)(CC(CN(C)C)C)C1=CC=CC=C1 XIGXDAPEMVTABC-UHFFFAOYSA-N 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 230000009935 nitrosation Effects 0.000 description 1
- 238000007034 nitrosation reaction Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 208000029340 primitive neuroectodermal tumor Diseases 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- FVLVBPDQNARYJU-UHFFFAOYSA-N semustine Chemical compound CC1CCC(NC(=O)N(CCCl)N=O)CC1 FVLVBPDQNARYJU-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- RBWSWDPRDBEWCR-RKJRWTFHSA-N sodium;(2r)-2-[(2r)-3,4-dihydroxy-5-oxo-2h-furan-2-yl]-2-hydroxyethanolate Chemical compound [Na+].[O-]C[C@@H](O)[C@H]1OC(=O)C(O)=C1O RBWSWDPRDBEWCR-RKJRWTFHSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7,934,307 | 1979-10-03 | ||
| GB7934307A GB2036377A (en) | 1978-10-04 | 1979-10-03 | A Control Apparatus |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1142183A true CA1142183A (fr) | 1983-03-01 |
Family
ID=10508261
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000361277A Expired CA1142183A (fr) | 1979-10-03 | 1980-09-30 | Derives de nitrosouree, compositions pharmaceutiques a base de ces derives et methode de preparation |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1142183A (fr) |
-
1980
- 1980-09-30 CA CA000361277A patent/CA1142183A/fr not_active Expired
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |