GB1592453A - Aminoalkyl esters of carbarimidothioic acid and compositions having immunosuppressant activity - Google Patents
Aminoalkyl esters of carbarimidothioic acid and compositions having immunosuppressant activity Download PDFInfo
- Publication number
- GB1592453A GB1592453A GB19994/76A GB1999476A GB1592453A GB 1592453 A GB1592453 A GB 1592453A GB 19994/76 A GB19994/76 A GB 19994/76A GB 1999476 A GB1999476 A GB 1999476A GB 1592453 A GB1592453 A GB 1592453A
- Authority
- GB
- United Kingdom
- Prior art keywords
- isothiourea
- formula
- pharmaceutically acceptable
- lower alkyl
- pharmaceutical composition
- 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
- 239000002253 acid Substances 0.000 title claims description 7
- 239000000203 mixture Substances 0.000 title description 25
- 230000001861 immunosuppressant effect Effects 0.000 title description 5
- 125000004103 aminoalkyl group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 15
- 239000000460 chlorine Substances 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 150000002541 isothioureas Chemical class 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 150000001721 carbon Chemical group 0.000 claims description 4
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 4
- 230000000699 topical effect Effects 0.000 claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 3
- 239000000470 constituent Substances 0.000 claims description 3
- 101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
- 239000007787 solid Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- -1 alkyl piperazine Chemical compound 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- RIHWDXYOYAYZBU-UHFFFAOYSA-N 2-(4,5-dihydro-1h-imidazol-2-ylsulfanyl)-n,n-dimethylethanamine Chemical class CN(C)CCSC1=NCCN1 RIHWDXYOYAYZBU-UHFFFAOYSA-N 0.000 description 3
- NYYRRBOMNHUCLB-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCCl NYYRRBOMNHUCLB-UHFFFAOYSA-N 0.000 description 3
- PDQAZBWRQCGBEV-UHFFFAOYSA-N Ethylenethiourea Chemical compound S=C1NCCN1 PDQAZBWRQCGBEV-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000012298 atmosphere 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
- 230000003111 delayed effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 3
- URUZINKWOOUTTH-UHFFFAOYSA-N 2-(4,5-dihydro-1h-imidazol-2-ylsulfanyl)-n,n-dimethylethanamine;dihydrochloride Chemical compound [Cl-].[Cl-].C[NH+](C)CCSC1=NCC[NH2+]1 URUZINKWOOUTTH-UHFFFAOYSA-N 0.000 description 2
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 2
- PYSGFFTXMUWEOT-UHFFFAOYSA-N 3-(dimethylamino)propan-1-ol Chemical compound CN(C)CCCO PYSGFFTXMUWEOT-UHFFFAOYSA-N 0.000 description 2
- BVCBJBVDMXCOJC-UHFFFAOYSA-N 3-(dimethylamino)propyl n,n'-dimethylcarbamimidothioate Chemical class CNC(=NC)SCCCN(C)C BVCBJBVDMXCOJC-UHFFFAOYSA-N 0.000 description 2
- VLCDUOXHFNUCKK-UHFFFAOYSA-N N,N'-Dimethylthiourea Chemical compound CNC(=S)NC VLCDUOXHFNUCKK-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 208000010247 contact dermatitis Diseases 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000008105 immune reaction Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 239000003226 mitogen Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- GHPYJLCQYMAXGG-WCCKRBBISA-N (2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid hydrochloride Chemical compound Cl.N[C@@H](CSCCB(O)O)C(O)=O GHPYJLCQYMAXGG-WCCKRBBISA-N 0.000 description 1
- SJHPCNCNNSSLPL-CSKARUKUSA-N (4e)-4-(ethoxymethylidene)-2-phenyl-1,3-oxazol-5-one Chemical compound O1C(=O)C(=C/OCC)\N=C1C1=CC=CC=C1 SJHPCNCNNSSLPL-CSKARUKUSA-N 0.000 description 1
- ZQGWBPQBZHMUFG-UHFFFAOYSA-N 1,1-dimethylthiourea Chemical compound CN(C)C(N)=S ZQGWBPQBZHMUFG-UHFFFAOYSA-N 0.000 description 1
- ZLJLVKBAMJHNJH-UHFFFAOYSA-N 1,3-diazepane-2-thione Chemical compound S=C1NCCCCN1 ZLJLVKBAMJHNJH-UHFFFAOYSA-N 0.000 description 1
- NVHNGVXBCWYLFA-UHFFFAOYSA-N 1,3-diazinane-2-thione Chemical compound S=C1NCCCN1 NVHNGVXBCWYLFA-UHFFFAOYSA-N 0.000 description 1
- FHDYRFNCTJFNQX-UHFFFAOYSA-N 1-(2-chloroethyl)-4-methylpiperazine Chemical compound CN1CCN(CCCl)CC1 FHDYRFNCTJFNQX-UHFFFAOYSA-N 0.000 description 1
- VFLQQZCRHPIGJU-UHFFFAOYSA-N 1-(2-chloroethyl)piperidine;hydron;chloride Chemical compound Cl.ClCCN1CCCCC1 VFLQQZCRHPIGJU-UHFFFAOYSA-N 0.000 description 1
- FFGFCSDCPGPSAJ-UHFFFAOYSA-N 1-ethyl-3-methylthiourea Chemical compound CCNC(=S)NC FFGFCSDCPGPSAJ-UHFFFAOYSA-N 0.000 description 1
- WRPJJYCUHPKEHF-UHFFFAOYSA-N 2-(dimethylamino)ethyl n,n'-dimethylcarbamimidothioate Chemical class CNC(=NC)SCCN(C)C WRPJJYCUHPKEHF-UHFFFAOYSA-N 0.000 description 1
- KMFBOMKUKPBRBH-UHFFFAOYSA-N 3-(4,5-dihydro-1h-imidazol-2-ylsulfanyl)-n,n-dimethylpropan-1-amine Chemical class CN(C)CCCSC1=NCCN1 KMFBOMKUKPBRBH-UHFFFAOYSA-N 0.000 description 1
- MTDFNKHFIYPIFF-UHFFFAOYSA-N 3-(4,5-dihydro-1h-imidazol-2-ylsulfanyl)-n,n-dimethylpropan-1-amine;dihydrochloride Chemical compound Cl.Cl.CN(C)CCCSC1=NCCN1 MTDFNKHFIYPIFF-UHFFFAOYSA-N 0.000 description 1
- DMPODMBXLRMZSP-UHFFFAOYSA-N 3-(dibutylamino)propan-1-ol Chemical compound CCCCN(CCCC)CCCO DMPODMBXLRMZSP-UHFFFAOYSA-N 0.000 description 1
- IBWVLACBTXBHAG-UHFFFAOYSA-N 3-(dibutylamino)propyl n,n'-dimethylcarbamimidothioate Chemical compound CCCCN(CCCC)CCCSC(NC)=NC IBWVLACBTXBHAG-UHFFFAOYSA-N 0.000 description 1
- IZBANMUQHMIFLD-UHFFFAOYSA-N 3-(methylamino)pentyl n-ethyl-n'-methylcarbamimidothioate Chemical compound CCNC(=NC)SCCC(CC)NC IZBANMUQHMIFLD-UHFFFAOYSA-N 0.000 description 1
- TZVYDYIDLQCRHV-UHFFFAOYSA-N 3-[ethyl(methyl)amino]propan-1-ol Chemical compound CCN(C)CCCO TZVYDYIDLQCRHV-UHFFFAOYSA-N 0.000 description 1
- NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 1
- UZGPYDPTSCLNEW-UHFFFAOYSA-N 4-(4,5-dihydro-1h-imidazol-2-ylsulfanyl)-n,n-dimethylbutan-1-amine Chemical compound CN(C)CCCCSC1=NCCN1 UZGPYDPTSCLNEW-UHFFFAOYSA-N 0.000 description 1
- LYHKQHLOZUTVKA-UHFFFAOYSA-N 4-chloro-n,n-dimethylbutan-1-amine Chemical compound CN(C)CCCCCl LYHKQHLOZUTVKA-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 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 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 239000004150 EU approved colour Substances 0.000 description 1
- 241001522296 Erithacus rubecula Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 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
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- KFFQABQEJATQAT-UHFFFAOYSA-N N,N'-dibutylthiourea Chemical compound CCCCNC(=S)NCCCC KFFQABQEJATQAT-UHFFFAOYSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229920003110 Primojel Polymers 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- UDIUIXIBBPOQKL-UHFFFAOYSA-N aziridine-1-carbothioamide Chemical compound NC(=S)N1CC1 UDIUIXIBBPOQKL-UHFFFAOYSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 210000003969 blast cell Anatomy 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- QYRFJLLXPINATB-UHFFFAOYSA-N hydron;2,4,5,6-tetrafluorobenzene-1,3-diamine;dichloride Chemical compound Cl.Cl.NC1=C(F)C(N)=C(F)C(F)=C1F QYRFJLLXPINATB-UHFFFAOYSA-N 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 150000002689 maleic acids Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 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
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000007916 tablet composition 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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/30—Isothioureas
- C07C335/32—Isothioureas having sulfur atoms of isothiourea groups bound to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/30—Oxygen or sulfur atoms
- C07D233/42—Sulfur atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Transplantation (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (27)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB19994/76A GB1592453A (en) | 1976-05-14 | 1976-05-14 | Aminoalkyl esters of carbarimidothioic acid and compositions having immunosuppressant activity |
| ZA00772612A ZA772612B (en) | 1976-05-14 | 1977-05-02 | Pharmaceutical compositions |
| FI771400A FI771400A7 (enExample) | 1976-05-14 | 1977-05-03 | |
| AT318277A AT359521B (de) | 1976-05-14 | 1977-05-04 | Verfahren zur herstellung von neuen isothio- harnstoffaminoalkylaethern sowie von deren salzen |
| PT66509A PT66509B (en) | 1976-05-14 | 1977-05-04 | Pharmaceutical compositions |
| IL52011A IL52011A (en) | 1976-05-14 | 1977-05-04 | Immunosuppressant pharmaceutical compositions containing 5-aminoalkyl isothiourea or 2-aminoalkyl imidazoline salts and some such novel compounds in the base or salt form |
| IE947/77A IE45144B1 (en) | 1976-05-14 | 1977-05-10 | Aminoalkyl esters of carbamimidothioic acid and compositions having immunosuppressant activity |
| CH589877A CH620203A5 (enExample) | 1976-05-14 | 1977-05-11 | |
| JP5483077A JPS532420A (en) | 1976-05-14 | 1977-05-11 | Isothiourea derivatives |
| AU25079/77A AU509573B2 (en) | 1976-05-14 | 1977-05-11 | Isothiourea derivatives |
| BE177510A BE854553A (fr) | 1976-05-14 | 1977-05-12 | Derives de l'isothiouree |
| AR267623A AR218872A1 (es) | 1976-05-14 | 1977-05-13 | Procedimiento para la preparacion de derivados de (n,n-dialquil(c1-c4)o pirrolidin-1-ilo,piperidin-1-ilo o morfolidin-1-ilo-alquil(c2-c4)-tio)-n,n-dialquil(c1-c4-isotiourea o imidazolin-2-ilo |
| HU77SI1576A HU174978B (hu) | 1976-05-14 | 1977-05-13 | Sposob poluchenija farmacevticheski aktivnykh proizvodnykh izotiokarbamida |
| FR7714766A FR2351098A1 (fr) | 1976-05-14 | 1977-05-13 | Derives de l'isothiouree, leur procede de preparation et leur application therapeutique |
| LU77332A LU77332A1 (enExample) | 1976-05-14 | 1977-05-13 | |
| DE19772721830 DE2721830A1 (de) | 1976-05-14 | 1977-05-13 | Arzneipraeparate mit einem gehalt an isothioharnstoffderivaten |
| CA278,412A CA1086758A (en) | 1976-05-14 | 1977-05-13 | Amino-alkyl-isothioureas and processes for their preparation |
| ES458756A ES458756A1 (es) | 1976-05-14 | 1977-05-13 | Procedimiento para preparar derivados de isotiourea. |
| NL7705331A NL7705331A (nl) | 1976-05-14 | 1977-05-13 | Werkwijze voor het bereiden van geneesmiddelen. |
| NO771697A NO771697L (no) | 1976-05-14 | 1977-05-13 | Fremgangsm}te for fremstilling av fysiologisk aktive isotiourinstoffer |
| DK211277A DK211277A (da) | 1976-05-14 | 1977-05-13 | Fremgangsmade til fremstilling af isothiourinstofderivater |
| SE7705658A SE7705658L (sv) | 1976-05-14 | 1977-05-16 | Farmaceutisk komposition |
| US05/853,773 US4205071A (en) | 1976-05-14 | 1977-11-21 | Pharmaceutical compositions having immunosuppressant activity and methods therefor |
| US06/082,836 US4294854A (en) | 1976-05-14 | 1979-10-09 | Pharmaceutical compositions |
| FR8024334A FR2472935A1 (fr) | 1976-05-14 | 1980-11-17 | Compositions pharmaceutiques ayant un effet immunodepresseur a base de derives de l'isothiouree |
| US06/269,248 US4378365A (en) | 1976-05-14 | 1981-06-01 | Pharmaceutical compositions |
| US06/655,197 US4649138A (en) | 1976-05-14 | 1984-09-28 | Pharmaceutical compositions |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB19994/76A GB1592453A (en) | 1976-05-14 | 1976-05-14 | Aminoalkyl esters of carbarimidothioic acid and compositions having immunosuppressant activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1592453A true GB1592453A (en) | 1981-07-08 |
Family
ID=10138568
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB19994/76A Expired GB1592453A (en) | 1976-05-14 | 1976-05-14 | Aminoalkyl esters of carbarimidothioic acid and compositions having immunosuppressant activity |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US4294854A (enExample) |
| JP (1) | JPS532420A (enExample) |
| AR (1) | AR218872A1 (enExample) |
| AT (1) | AT359521B (enExample) |
| AU (1) | AU509573B2 (enExample) |
| BE (1) | BE854553A (enExample) |
| CA (1) | CA1086758A (enExample) |
| CH (1) | CH620203A5 (enExample) |
| DE (1) | DE2721830A1 (enExample) |
| DK (1) | DK211277A (enExample) |
| ES (1) | ES458756A1 (enExample) |
| FI (1) | FI771400A7 (enExample) |
| FR (2) | FR2351098A1 (enExample) |
| GB (1) | GB1592453A (enExample) |
| HU (1) | HU174978B (enExample) |
| IE (1) | IE45144B1 (enExample) |
| IL (1) | IL52011A (enExample) |
| LU (1) | LU77332A1 (enExample) |
| NL (1) | NL7705331A (enExample) |
| NO (1) | NO771697L (enExample) |
| PT (1) | PT66509B (enExample) |
| SE (1) | SE7705658L (enExample) |
| ZA (1) | ZA772612B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5556754A (en) * | 1993-06-07 | 1996-09-17 | The United States Of America As Represented By The Department Of Health And Human Services | Methods for assessing the ability of a candidate drug to suppress MHC class I expression |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0672244B2 (ja) * | 1984-12-12 | 1994-09-14 | 三菱マテリアル株式会社 | 貴金属造粒装置 |
| WO1996006076A1 (en) * | 1994-08-18 | 1996-02-29 | Chugai Seiyaku Kabushiki Kaisha | Amino acid derivative having nitrogen monoxide synthetase inhibitor activity |
| US7645873B2 (en) * | 2003-03-20 | 2010-01-12 | The Scripps Research Institute | 6″-amino-6″-deoxygalactosylceramides |
| EP2058011A1 (en) * | 2007-11-07 | 2009-05-13 | Wittycell | Nkt cell activating gycolipids covalently bound antigens and/or drug |
| CN102215864A (zh) * | 2008-10-08 | 2011-10-12 | 威蒂赛尔公司 | 用于抗流感的疫苗组合物 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2648710A (en) * | 1950-09-22 | 1953-08-11 | Hoffmann La Roche | Bis-quaternary salts of 1:10-bis-(dialkylamino)-5:6-dithia-decane |
| US2813102A (en) * | 1956-04-10 | 1957-11-12 | American Home Prod | 2-(di-lower alkylaminoethylmercapto)-imidazolines and their acid addition salts and preparation thereof |
| US4152453A (en) * | 1975-12-01 | 1979-05-01 | Smith Kline & French Laboratories Limited | Pharmacologically active compounds and compositions and methods of use |
-
1976
- 1976-05-14 GB GB19994/76A patent/GB1592453A/en not_active Expired
-
1977
- 1977-05-02 ZA ZA00772612A patent/ZA772612B/xx unknown
- 1977-05-03 FI FI771400A patent/FI771400A7/fi not_active Application Discontinuation
- 1977-05-04 IL IL52011A patent/IL52011A/xx unknown
- 1977-05-04 PT PT66509A patent/PT66509B/pt unknown
- 1977-05-04 AT AT318277A patent/AT359521B/de not_active IP Right Cessation
- 1977-05-10 IE IE947/77A patent/IE45144B1/en unknown
- 1977-05-11 JP JP5483077A patent/JPS532420A/ja active Pending
- 1977-05-11 CH CH589877A patent/CH620203A5/fr not_active IP Right Cessation
- 1977-05-11 AU AU25079/77A patent/AU509573B2/en not_active Expired
- 1977-05-12 BE BE177510A patent/BE854553A/xx not_active IP Right Cessation
- 1977-05-13 DE DE19772721830 patent/DE2721830A1/de not_active Withdrawn
- 1977-05-13 NL NL7705331A patent/NL7705331A/xx not_active Application Discontinuation
- 1977-05-13 DK DK211277A patent/DK211277A/da not_active Application Discontinuation
- 1977-05-13 LU LU77332A patent/LU77332A1/xx unknown
- 1977-05-13 AR AR267623A patent/AR218872A1/es active
- 1977-05-13 HU HU77SI1576A patent/HU174978B/hu unknown
- 1977-05-13 NO NO771697A patent/NO771697L/no unknown
- 1977-05-13 FR FR7714766A patent/FR2351098A1/fr active Granted
- 1977-05-13 ES ES458756A patent/ES458756A1/es not_active Expired
- 1977-05-13 CA CA278,412A patent/CA1086758A/en not_active Expired
- 1977-05-16 SE SE7705658A patent/SE7705658L/xx unknown
-
1979
- 1979-10-09 US US06/082,836 patent/US4294854A/en not_active Expired - Lifetime
-
1980
- 1980-11-17 FR FR8024334A patent/FR2472935A1/fr not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5556754A (en) * | 1993-06-07 | 1996-09-17 | The United States Of America As Represented By The Department Of Health And Human Services | Methods for assessing the ability of a candidate drug to suppress MHC class I expression |
| US5871950A (en) * | 1993-06-07 | 1999-02-16 | Singer; Dinah S. | Methods of treating autoimmune diseases and transplantation rejection |
Also Published As
| Publication number | Publication date |
|---|---|
| IE45144B1 (en) | 1982-06-30 |
| JPS532420A (en) | 1978-01-11 |
| SE7705658L (sv) | 1977-11-15 |
| AU509573B2 (en) | 1980-05-15 |
| ES458756A1 (es) | 1978-03-01 |
| BE854553A (fr) | 1977-11-14 |
| DK211277A (da) | 1977-11-15 |
| FR2351098A1 (fr) | 1977-12-09 |
| US4294854A (en) | 1981-10-13 |
| DE2721830A1 (de) | 1977-11-24 |
| AU2507977A (en) | 1978-11-16 |
| AT359521B (de) | 1980-11-10 |
| HU174978B (hu) | 1980-04-28 |
| IE45144L (en) | 1977-11-14 |
| ATA318277A (de) | 1980-04-15 |
| IL52011A (en) | 1982-05-31 |
| AR218872A1 (es) | 1980-07-15 |
| FR2351098B1 (enExample) | 1982-06-18 |
| LU77332A1 (enExample) | 1977-08-29 |
| FI771400A7 (enExample) | 1977-11-15 |
| ZA772612B (en) | 1978-04-26 |
| NL7705331A (nl) | 1977-11-16 |
| PT66509A (en) | 1977-06-01 |
| PT66509B (en) | 1978-10-16 |
| NO771697L (no) | 1977-11-15 |
| CH620203A5 (enExample) | 1980-11-14 |
| CA1086758A (en) | 1980-09-30 |
| FR2472935A1 (fr) | 1981-07-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US3669968A (en) | Trialkoxy quinazolines | |
| US3505350A (en) | Certain substituted 2-mercaptoimidazole derivatives | |
| US4343804A (en) | 4-Amino-3-quinolinecarboxylic acids and esters-antisecretory anti-ulcer compounds | |
| EP0005205B1 (de) | Substituierte 5,6-Dimethylpyrrolo(2,3-d)pyrimidine, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel | |
| JPS5946221B2 (ja) | 複素環化合物の製法 | |
| DE3441975C2 (enExample) | ||
| KR100447033B1 (ko) | 신규한2-나프타미드유도체와이의치료제로서의사용 | |
| US3862139A (en) | Heterocyclic benzamide compounds | |
| GB2101589A (en) | Crystalline benzothiazine dioxide salts. | |
| JPS5830314B2 (ja) | グアニジン化合物の製法 | |
| EP0219292A2 (en) | Use of indolobenzodiazepines for antagonizing luteinizing hormone releasing hormone | |
| US4179563A (en) | 3-Aryloxy-substituted-aminopyridines and methods for their production | |
| KR930007413B1 (ko) | 새로운 피리딜- 및 피리미딜 유도체와 약리학적으로 활성인 그의 염 및 그 제조방법과 이들을 이용한 사람 이외의 온혈동물의 정신장해 치료방법 | |
| US3868457A (en) | Method of inhibiting histamine activity with guanidine compounds | |
| JPH0226629B2 (enExample) | ||
| US3579524A (en) | 2-aminoalkyl derivatives of phthalimidines | |
| EP0221511B1 (en) | 2-aminosulfonyl-6-nitrobenzoic esters or amides, process for their preparation and pharmaceutical compositions containing them | |
| DD143255A5 (de) | Verfahren zur herstellung von substituierten 1,3-diaryl-2-imino-imidazolidinen und -2-imino-hexa-hydropyrimidinen | |
| GB1592453A (en) | Aminoalkyl esters of carbarimidothioic acid and compositions having immunosuppressant activity | |
| DE69311566T2 (de) | Heterocyclische amine als calmodulin antagonisten | |
| JPS5946220B2 (ja) | 複素環化合物の製法 | |
| EP0093252B1 (de) | Thiomethylpyridin-Derivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| US4205071A (en) | Pharmaceutical compositions having immunosuppressant activity and methods therefor | |
| US3299090A (en) | Nitroimidazoles | |
| US4113868A (en) | 5,6-dihydropyrimidin-4(3h)one derivatives, and antiedema compositions and methods employing them |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed [section 19, patents act 1949] | ||
| PCNP | Patent ceased through non-payment of renewal fee |