CA1096384A - Preparation of amidino and guanidino phosphonates - Google Patents

Preparation of amidino and guanidino phosphonates

Info

Publication number: CA1096384A
Authority: CA; Canada
Prior art keywords: methyl; het; lower alkyl; hydrogen; imidazolyl
Prior art date: 1977-06-02
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

CA304,575A

Other languages

English (en)

French (fr)

Inventor

Graham J. Durant

Rodney C. Young

Zev Tashma

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.)

Smith Kline and French Laboratories Ltd

Original Assignee

Smith Kline and French Laboratories 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.)

1977-06-02

Filing date

1978-06-01

Publication date

1981-02-24

1978-06-01 Application filed by Smith Kline and French Laboratories Ltd filed Critical Smith Kline and French Laboratories Ltd

1981-02-24 Application granted granted Critical

1981-02-24 Publication of CA1096384A publication Critical patent/CA1096384A/en

Status Expired legal-status Critical Current

Links

238000002360 preparation method Methods 0.000 title abstract description 5
OPPOXKMNNALLOI-UHFFFAOYSA-N NC(NOP(O)=O)=N Chemical class NC(NOP(O)=O)=N OPPOXKMNNALLOI-UHFFFAOYSA-N 0.000 title 1
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 title 1
-1 Amidine phosphonate compounds Chemical class 0.000 claims abstract description 47
125000000217 alkyl group Chemical group 0.000 claims abstract description 47
150000001875 compounds Chemical class 0.000 claims abstract description 47
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 38
239000001257 hydrogen Substances 0.000 claims abstract description 37
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 15
239000005864 Sulphur Substances 0.000 claims abstract description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
150000002431 hydrogen Chemical group 0.000 claims abstract description 13
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 11
238000000034 method Methods 0.000 claims description 52
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
238000006243 chemical reaction Methods 0.000 claims description 20
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 10
239000000126 substance Substances 0.000 claims description 9
125000000623 heterocyclic group Chemical group 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical group 0.000 claims description 7
125000002883 imidazolyl group Chemical group 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 4
239000007795 chemical reaction product Substances 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
150000001721 carbon Chemical group 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
230000000295 complement effect Effects 0.000 claims description 2
230000003301 hydrolyzing effect Effects 0.000 claims description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 4
125000000335 thiazolyl group Chemical group 0.000 claims 2
125000003118 aryl group Chemical group 0.000 abstract description 22
230000007062 hydrolysis Effects 0.000 abstract description 11
238000006460 hydrolysis reaction Methods 0.000 abstract description 11
239000003485 histamine H2 receptor antagonist Substances 0.000 abstract description 6
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 abstract description 6
238000005859 coupling reaction Methods 0.000 abstract description 5
239000000543 intermediate Substances 0.000 abstract description 5
230000000694 effects Effects 0.000 abstract description 4
239000004480 active ingredient Substances 0.000 abstract description 3
239000008194 pharmaceutical composition Substances 0.000 abstract description 3
238000005954 phosphonylation reaction Methods 0.000 abstract 1
150000003141 primary amines Chemical class 0.000 abstract 1
239000003153 chemical reaction reagent Substances 0.000 description 30
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
239000002253 acid Substances 0.000 description 20
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 13
229960001340 histamine Drugs 0.000 description 12
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 10
150000003839 salts Chemical class 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
239000000460 chlorine Substances 0.000 description 8
229910052801 chlorine Inorganic materials 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
JEOZNMMOIBLWLV-UHFFFAOYSA-N 2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethanamine Chemical compound CC=1N=CNC=1CSCCN JEOZNMMOIBLWLV-UHFFFAOYSA-N 0.000 description 7
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 7
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 7
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
230000031018 biological processes and functions Effects 0.000 description 6
150000005690 diesters Chemical class 0.000 description 6
239000000047 product Substances 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
102000003710 Histamine H2 Receptors Human genes 0.000 description 5
108090000050 Histamine H2 Receptors Proteins 0.000 description 5
125000001309 chloro group Chemical group Cl* 0.000 description 5
229910000042 hydrogen bromide Inorganic materials 0.000 description 5
238000003756 stirring Methods 0.000 description 5
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 5
QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
LGDSHSYDSCRFAB-UHFFFAOYSA-N Methyl isothiocyanate Chemical compound CN=C=S LGDSHSYDSCRFAB-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
239000007788 liquid Substances 0.000 description 4
239000000203 mixture Substances 0.000 description 4
239000007787 solid Substances 0.000 description 4
ITAMCOCNZJPJDF-UHFFFAOYSA-N 1-(6-aminopurin-9-yl)propan-2-yloxymethyl-phenoxyphosphinic acid Chemical compound C1=NC2=C(N)N=CN=C2N1CC(C)OCP(O)(=O)OC1=CC=CC=C1 ITAMCOCNZJPJDF-UHFFFAOYSA-N 0.000 description 3
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
UDUMWDDMSHXGGQ-UHFFFAOYSA-N [amino(methylsulfanyl)methylidene]-methylazanium;iodide Chemical compound I.CSC(N)=NC UDUMWDDMSHXGGQ-UHFFFAOYSA-N 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
239000000739 antihistaminic agent Substances 0.000 description 3
229940125715 antihistaminic agent Drugs 0.000 description 3
235000010290 biphenyl Nutrition 0.000 description 3
239000004305 biphenyl Substances 0.000 description 3
RIMGDBZXWSGBQN-UHFFFAOYSA-N burimamide Chemical compound CNC(=S)NCCCCC1=CN=C[N]1 RIMGDBZXWSGBQN-UHFFFAOYSA-N 0.000 description 3
WJOZHMLTXAXJGX-UHFFFAOYSA-N chloro(3-phenylpropoxy)phosphinic acid Chemical compound OP(Cl)(=O)OCCCC1=CC=CC=C1 WJOZHMLTXAXJGX-UHFFFAOYSA-N 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
238000001816 cooling Methods 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
230000001404 mediated effect Effects 0.000 description 3
NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
RQKYHDHLEMEVDR-UHFFFAOYSA-N oxo-bis(phenylmethoxy)phosphanium Chemical compound C=1C=CC=CC=1CO[P+](=O)OCC1=CC=CC=C1 RQKYHDHLEMEVDR-UHFFFAOYSA-N 0.000 description 3
ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
YZBOZNXACBQJHI-UHFFFAOYSA-N 1-dichlorophosphoryloxyethane Chemical compound CCOP(Cl)(Cl)=O YZBOZNXACBQJHI-UHFFFAOYSA-N 0.000 description 2
QEBVWWWCJJNGRP-UHFFFAOYSA-N 2-(1,3,4-thiadiazol-2-ylmethylsulfanyl)ethanamine Chemical compound NCCSCC1=NN=CS1 QEBVWWWCJJNGRP-UHFFFAOYSA-N 0.000 description 2
BUTQLNVJGRJSAE-UHFFFAOYSA-N 2-(1h-1,2,4-triazol-5-ylmethylsulfanyl)ethanamine Chemical compound NCCSCC=1N=CNN=1 BUTQLNVJGRJSAE-UHFFFAOYSA-N 0.000 description 2
CNMUGSJVSYLQOX-UHFFFAOYSA-N 2-(1h-imidazol-5-ylmethylsulfanyl)ethanamine Chemical compound NCCSCC1=CNC=N1 CNMUGSJVSYLQOX-UHFFFAOYSA-N 0.000 description 2
XZXYQEHISUMZAT-UHFFFAOYSA-N 2-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol Chemical compound CC1=CC=C(O)C(CC=2C(=CC=C(C)C=2)O)=C1 XZXYQEHISUMZAT-UHFFFAOYSA-N 0.000 description 2
HTABEAIBEITBJS-UHFFFAOYSA-N 2-[(3-chloropyridin-2-yl)methylsulfanyl]ethanamine Chemical compound NCCSCC1=NC=CC=C1Cl HTABEAIBEITBJS-UHFFFAOYSA-N 0.000 description 2
NTLFEXLXZRBDPP-UHFFFAOYSA-N 2-[(4-bromo-1h-imidazol-5-yl)methylsulfanyl]ethanamine Chemical compound NCCSCC=1NC=NC=1Br NTLFEXLXZRBDPP-UHFFFAOYSA-N 0.000 description 2
VJSUMPPMFYQOMP-UHFFFAOYSA-N 4-(1h-imidazol-5-yl)butan-1-amine Chemical compound NCCCCC1=CNC=N1 VJSUMPPMFYQOMP-UHFFFAOYSA-N 0.000 description 2
241000700199 Cavia porcellus Species 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
229940107816 ammonium iodide Drugs 0.000 description 2
235000019445 benzyl alcohol Nutrition 0.000 description 2
230000036772 blood pressure Effects 0.000 description 2
239000000969 carrier Substances 0.000 description 2
230000008878 coupling Effects 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
125000004185 ester group Chemical group 0.000 description 2
125000004494 ethyl ester group Chemical group 0.000 description 2
210000004211 gastric acid Anatomy 0.000 description 2
230000027119 gastric acid secretion Effects 0.000 description 2
210000002837 heart atrium Anatomy 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
125000004356 hydroxy functional group Chemical group O* 0.000 description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
230000005764 inhibitory process Effects 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
YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 2
229960000582 mepyramine Drugs 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
239000003208 petroleum Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
238000010992 reflux Methods 0.000 description 2
102200014657 rs121434437 Human genes 0.000 description 2
230000028327 secretion Effects 0.000 description 2
NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
150000003512 tertiary amines Chemical class 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
LPKCJFLRJWWIDI-UHFFFAOYSA-N (diaminomethylideneamino)phosphonic acid Chemical class NC(N)=NP(O)(O)=O LPKCJFLRJWWIDI-UHFFFAOYSA-N 0.000 description 1
DHZAPGYTQSDHAA-UHFFFAOYSA-N 1-[ethoxy(phenylmethoxy)phosphoryl]-1,2-dimethyl-3-[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethyl]guanidine Chemical compound N1=CNC(C)=C1CSCCNC(=NC)N(C)P(=O)(OCC)OCC1=CC=CC=C1 DHZAPGYTQSDHAA-UHFFFAOYSA-N 0.000 description 1
JBGXWNBKQNLZOP-UHFFFAOYSA-N 1-[ethoxy(phenylmethoxy)phosphoryl]-2,3-bis[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethyl]guanidine Chemical compound C=1C=CC=CC=1COP(=O)(OCC)NC(=NCCSCC1=C(NC=N1)C)NCCSCC=1N=CNC=1C JBGXWNBKQNLZOP-UHFFFAOYSA-N 0.000 description 1
JNIZZUYHDUWKGQ-UHFFFAOYSA-N 1-bis(phenylmethoxy)phosphoryl-2-methyl-3-[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethyl]guanidine Chemical compound C=1C=CC=CC=1COP(=O)(OCC=1C=CC=CC=1)NC(=NC)NCCSCC=1N=CNC=1C JNIZZUYHDUWKGQ-UHFFFAOYSA-N 0.000 description 1
GKIUPDRWOXMZDT-UHFFFAOYSA-N 2-(1,2-thiazol-3-ylmethylsulfanyl)ethanamine Chemical compound NCCSCC=1C=CSN=1 GKIUPDRWOXMZDT-UHFFFAOYSA-N 0.000 description 1
IXFKWSLOVDXTFU-UHFFFAOYSA-N 2-(1,3-oxazol-2-ylmethylsulfanyl)ethanamine Chemical compound NCCSCC1=NC=CO1 IXFKWSLOVDXTFU-UHFFFAOYSA-N 0.000 description 1
WAIHMWWSWLOHNH-UHFFFAOYSA-N 2-(1,3-thiazol-2-ylmethylsulfanyl)ethanamine Chemical compound NCCSCC1=NC=CS1 WAIHMWWSWLOHNH-UHFFFAOYSA-N 0.000 description 1
YJGPAHTYRHCODQ-UHFFFAOYSA-N 2-(1,3-thiazol-2-ylmethylsulfanyl)ethanamine;dihydrobromide Chemical compound Br.Br.NCCSCC1=NC=CS1 YJGPAHTYRHCODQ-UHFFFAOYSA-N 0.000 description 1
VGMZAKKUIGITCD-UHFFFAOYSA-N 2-[(3-methoxypyridin-2-yl)methylsulfanyl]ethanamine Chemical compound COC1=CC=CN=C1CSCCN VGMZAKKUIGITCD-UHFFFAOYSA-N 0.000 description 1
HYSZRUJKUKKFRL-UHFFFAOYSA-N 2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]propan-1-amine Chemical compound NCC(C)SCC=1N=CNC=1C HYSZRUJKUKKFRL-UHFFFAOYSA-N 0.000 description 1
MTIMDGQILFWMJI-UHFFFAOYSA-N 2-methylsulfanyl-4,5-dihydro-1h-imidazole Chemical compound CSC1=NCCN1 MTIMDGQILFWMJI-UHFFFAOYSA-N 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
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240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
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108010079943 Pentagastrin Proteins 0.000 description 1
101100313649 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) POT1 gene Proteins 0.000 description 1
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QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
208000001871 Tachycardia Diseases 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
101100161758 Yarrowia lipolytica (strain CLIB 122 / E 150) POX3 gene Proteins 0.000 description 1
CMALSAKGWMXXGV-UHFFFAOYSA-N [[N'-methyl-N-[2-(1,3,4-thiadiazol-2-ylmethylsulfanyl)ethyl]carbamimidoyl]amino]phosphonic acid Chemical compound OP(=O)(O)NC(=NC)NCCSCC1=NN=CS1 CMALSAKGWMXXGV-UHFFFAOYSA-N 0.000 description 1
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GPEGHMAERWEZIX-UHFFFAOYSA-N [[n'-methyl-n-[2-(1,3-thiazol-2-ylmethylsulfanyl)ethyl]carbamimidoyl]amino]phosphonic acid Chemical compound OP(=O)(O)NC(=NC)NCCSCC1=NC=CS1 GPEGHMAERWEZIX-UHFFFAOYSA-N 0.000 description 1
DJHIVLSHUBMRDJ-UHFFFAOYSA-N [[n'-methyl-n-[2-(1h-1,2,4-triazol-5-ylmethylsulfanyl)ethyl]carbamimidoyl]amino]phosphonic acid Chemical compound OP(=O)(O)NC(=NC)NCCSCC1=NC=NN1 DJHIVLSHUBMRDJ-UHFFFAOYSA-N 0.000 description 1
UKVHKQOWTUNYBU-UHFFFAOYSA-N [[n'-methyl-n-[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethyl]carbamimidoyl]amino]phosphonic acid Chemical compound OP(=O)(O)NC(=NC)NCCSCC=1N=CNC=1C UKVHKQOWTUNYBU-UHFFFAOYSA-N 0.000 description 1
RKPUDJSDRKFZRP-UHFFFAOYSA-N [[n-[2-(1h-imidazol-5-ylmethylsulfanyl)ethyl]-n'-methylcarbamimidoyl]amino]phosphonic acid Chemical compound OP(=O)(O)NC(=NC)NCCSCC1=CN=CN1 RKPUDJSDRKFZRP-UHFFFAOYSA-N 0.000 description 1
BHGMJEOZUJHOPW-UHFFFAOYSA-N [[n-[2-[(4-bromo-1h-imidazol-5-yl)methylsulfanyl]ethyl]-n'-methylcarbamimidoyl]amino]phosphonic acid Chemical compound OP(=O)(O)NC(=NC)NCCSCC=1NC=NC=1Br BHGMJEOZUJHOPW-UHFFFAOYSA-N 0.000 description 1
HKYNYPZMYYWCFH-UHFFFAOYSA-N [[n-[4-(1h-imidazol-5-yl)butyl]-n'-methylcarbamimidoyl]amino]phosphonic acid Chemical compound OP(=O)(O)NC(=NC)NCCCCC1=CN=CN1 HKYNYPZMYYWCFH-UHFFFAOYSA-N 0.000 description 1
NMRWMSCNEQEIMM-UHFFFAOYSA-N [n'-methyl-n-[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethyl]carbamimidoyl]phosphonic acid Chemical compound CNC(P(O)(O)=O)=NCCSCC=1N=CNC=1C NMRWMSCNEQEIMM-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000013543 active substance Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
239000003708 ampul Substances 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
239000011260 aqueous acid Substances 0.000 description 1
125000004104 aryloxy group Chemical group 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
MRKFHQKLPMGVJD-UHFFFAOYSA-N benzyl phenyl hydrogen phosphite Chemical compound C=1C=CC=CC=1OP(O)OCC1=CC=CC=C1 MRKFHQKLPMGVJD-UHFFFAOYSA-N 0.000 description 1
238000009835 boiling Methods 0.000 description 1
102220347004 c.89G>A Human genes 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
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238000007796 conventional method Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
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LXHWDUISRBUGRA-UHFFFAOYSA-N dichloro(phenoxy)phosphane Chemical compound ClP(Cl)OC1=CC=CC=C1 LXHWDUISRBUGRA-UHFFFAOYSA-N 0.000 description 1
TXFOLHZMICYNRM-UHFFFAOYSA-N dichlorophosphoryloxybenzene Chemical compound ClP(Cl)(=O)OC1=CC=CC=C1 TXFOLHZMICYNRM-UHFFFAOYSA-N 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
229960000520 diphenhydramine Drugs 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
239000002552 dosage form Substances 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
239000000839 emulsion Substances 0.000 description 1
HGRAEDKYZOPIQQ-UHFFFAOYSA-N ethoxy-[n'-methyl-n-[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethyl]carbamimidoyl]phosphinic acid Chemical compound CCOP(O)(=O)C(NC)=NCCSCC=1N=CNC=1C HGRAEDKYZOPIQQ-UHFFFAOYSA-N 0.000 description 1
LEPCRJVSNJIRIX-UHFFFAOYSA-N ethoxy-n-methyl-n-[n'-methyl-n-[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethyl]carbamimidoyl]phosphonamidic acid Chemical compound CCOP(O)(=O)N(C)C(=NC)NCCSCC=1N=CNC=1C LEPCRJVSNJIRIX-UHFFFAOYSA-N 0.000 description 1
UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 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
238000001914 filtration Methods 0.000 description 1
235000013305 food Nutrition 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
LFXAECSQJSRSTP-UHFFFAOYSA-N hydron;methyl carbamimidothioate;iodide Chemical compound I.CSC(N)=N LFXAECSQJSRSTP-UHFFFAOYSA-N 0.000 description 1
125000002636 imidazolinyl group Chemical group 0.000 description 1
125000001841 imino group Chemical group [H]N=* 0.000 description 1
239000012535 impurity Substances 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
230000010354 integration Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
150000002540 isothiocyanates Chemical class 0.000 description 1
150000002541 isothioureas Chemical class 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 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
235000019359 magnesium stearate Nutrition 0.000 description 1
150000002689 maleic acids Chemical class 0.000 description 1
238000005259 measurement Methods 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
PFJMWGUDKKPHFR-UHFFFAOYSA-N methyl n,n-dimethylcarbamimidothioate;hydroiodide Chemical compound I.CSC(=N)N(C)C PFJMWGUDKKPHFR-UHFFFAOYSA-N 0.000 description 1
CEDDCYUKMGOTCW-UHFFFAOYSA-N methyl n-bis(phenylmethoxy)phosphoryl-n'-methylcarbamimidothioate Chemical compound C=1C=CC=CC=1COP(=O)(N=C(SC)NC)OCC1=CC=CC=C1 CEDDCYUKMGOTCW-UHFFFAOYSA-N 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
LGVXHBNICWGKGM-UHFFFAOYSA-N n-(n-methyl-c-methylsulfanylcarbonimidoyl)-(3-phenylpropoxy)phosphonamidic acid Chemical compound CNC(SC)=NP(O)(=O)OCCCC1=CC=CC=C1 LGVXHBNICWGKGM-UHFFFAOYSA-N 0.000 description 1
IHJFGFWDSZKVOV-UHFFFAOYSA-N n-[n'-methyl-n-[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethyl]carbamimidoyl]-phenylmethoxyphosphonamidic acid;hydrobromide Chemical compound Br.C=1C=CC=CC=1COP(O)(=O)NC(=NC)NCCSCC=1N=CNC=1C IHJFGFWDSZKVOV-UHFFFAOYSA-N 0.000 description 1
UBOLWIVYXVBPAJ-UHFFFAOYSA-N n-[n,n'-bis[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethyl]carbamimidoyl]-ethoxyphosphonamidic acid Chemical compound N1=CNC(C)=C1CSCCN=C(NP(O)(=O)OCC)NCCSCC=1N=CNC=1C UBOLWIVYXVBPAJ-UHFFFAOYSA-N 0.000 description 1
YKSCEVSPNVUFAW-UHFFFAOYSA-N n-methyl-1-[phenoxy(phenylmethoxy)phosphoryl]methanethioamide Chemical compound C=1C=CC=CC=1OP(=O)(C(=S)NC)OCC1=CC=CC=C1 YKSCEVSPNVUFAW-UHFFFAOYSA-N 0.000 description 1
238000006386 neutralization reaction Methods 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
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
125000000962 organic group Chemical group 0.000 description 1
239000003960 organic solvent 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
ANRIQLNBZQLTFV-DZUOILHNSA-N pentagastrin Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1[C]2C=CC=CC2=NC=1)NC(=O)CCNC(=O)OC(C)(C)C)CCSC)C(N)=O)C1=CC=CC=C1 ANRIQLNBZQLTFV-DZUOILHNSA-N 0.000 description 1
229960000444 pentagastrin Drugs 0.000 description 1
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical class [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
150000003018 phosphorus compounds Chemical class 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
229910001923 silver oxide Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000001117 sulphuric acid Substances 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
230000006794 tachycardia Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
238000012360 testing method Methods 0.000 description 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
210000004291 uterus Anatomy 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1

CA304,575A 1977-06-02 1978-06-01 Preparation of amidino and guanidino phosphonates Expired CA1096384A (en)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GB23423/77		1977-06-02
GB2342377		1977-06-02
GB39118/77		1977-09-20
GB3911877		1977-09-20

Publications (1)

Publication Number	Publication Date
CA1096384A true CA1096384A (en)	1981-02-24

Family

ID=26256502

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA304,575A Expired CA1096384A (en)	1977-06-02	1978-06-01	Preparation of amidino and guanidino phosphonates

Country Status (12)

Country	Link
JP (1)	JPS543068A (de)
AT (1)	AT369013B (de)
AU (1)	AU514526B2 (de)
CA (1)	CA1096384A (de)
DK (1)	DK245078A (de)
FI (1)	FI781714A7 (de)
HU (1)	HU177898B (de)
IE (1)	IE47275B1 (de)
IL (1)	IL54832A (de)
IT (1)	IT7824126A0 (de)
NO (1)	NO781914L (de)
ZA (1)	ZA783118B (de)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IE53068B1 (en) *	1981-06-15	1988-05-25	Merck & Co Inc	Diamino isothiazole-1-oxides and -1,1-dioxides as gastic secretion inhibitors
JP7068507B2 (ja)	2019-01-23	2022-05-16	株式会社東芝	電力供給システム、及び電力供給システムの制御方法

1978
- 1978-05-30 FI FI781714A patent/FI781714A7/fi not_active Application Discontinuation
- 1978-05-30 ZA ZA00783118A patent/ZA783118B/xx unknown
- 1978-05-31 AU AU36746/78A patent/AU514526B2/en not_active Expired
- 1978-05-31 IE IE110078A patent/IE47275B1/en unknown
- 1978-06-01 IL IL54832A patent/IL54832A/xx unknown
- 1978-06-01 CA CA304,575A patent/CA1096384A/en not_active Expired
- 1978-06-01 IT IT7824126A patent/IT7824126A0/it unknown
- 1978-06-01 DK DK245078A patent/DK245078A/da unknown
- 1978-06-01 NO NO781914A patent/NO781914L/no unknown
- 1978-06-01 HU HUSI001630 patent/HU177898B/hu unknown
- 1978-06-02 AT AT403078A patent/AT369013B/de not_active IP Right Cessation
- 1978-06-02 JP JP6716978A patent/JPS543068A/ja active Pending

Also Published As

Publication number	Publication date
IE781100L (en)	1978-12-02
FI781714A7 (fi)	1978-12-03
HU177898B (en)	1982-01-28
AU3674678A (en)	1979-12-06
AU514526B2 (en)	1981-02-12
NO781914L (no)	1978-12-05
DK245078A (da)	1978-12-03
JPS543068A (en)	1979-01-11
AT369013B (de)	1982-11-25
ZA783118B (en)	1979-06-27
ATA403078A (de)	1982-04-15
IL54832A (en)	1983-07-31
IE47275B1 (en)	1984-02-08
IL54832A0 (en)	1978-08-31
IT7824126A0 (it)	1978-06-01

Legal Events

Date	Code	Title	Description
1998-02-24	MKEX	Expiry

Publication	Publication Date	Title
US4746654A (en)	1988-05-24	Anti-inflammatory products derived from methylene-diphosphonic acid, and process for their preparation
US4939130A (en)	1990-07-03	Substituted alkanediphosphonic acids and pharmaceutical use
KR100366727B1 (ko)	2003-03-15	포스포네이트뉴클레오티드화합물
KR0156239B1 (ko)	1998-12-01	헤테로 사이클릭 비스포스폰산 유도체 및 이의 제조방법
EP0070433A1 (de)	1983-01-26	Phospholipide Derivate, Verfahren zu ihrer Herstellung und sie enthaltende pharmazeutische Zubereitungen
SI9520067A (en)	1997-10-31	Phosphinic acid derivates with metallopeptidase inhibitory activity.
CS244408B2 (en)	1986-07-17	Method of n-phosphonomethylglycine production
CA1096384A (en)	1981-02-24	Preparation of amidino and guanidino phosphonates
EP0007326B1 (de)	1982-01-27	Amidine, deren Herstellung und diese Amidine enthaltende pharmazeutische Zusammensetzungen.
US4190664A (en)	1980-02-26	Amidino and guanidino phosphonates
US4282213A (en)	1981-08-04	Amidino and guanidino phosphonates
US5155099A (en)	1992-10-13	Alkylphosphonoserines and pharmaceutical compositions useful as cytostatic agents
EP0518861B1 (de)	1994-09-14	Verfahren zur gewinnung von phosphorigsäure-bis-(2,4-di-tert.-butyl-phenyl)-ester-halogeniden
US5245069A (en)	1993-09-14	Process for the preparation of bis(aryl)-phosphorohalidates
CA1052810A (en)	1979-04-17	.omega.-(N-ACYLAMINO) ALKYLPHOSPHORYL ETHANOLAMINES, PROCESS FOR PREPARING THEM, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND THEIR USES
US5679842A (en)	1997-10-21	Process for the preparation of aminomethanephosphonic acid and aminomethylphosphinic acids
US5057505A (en)	1991-10-15	Substituted aminomethanediphosphonic acids and use in medicaments
EP1012152B1 (de)	2002-10-09	Verfahren zur herstellung von oxazaphosphorin-2-aminen
CA1324383C (en)	1993-11-16	Process for the manufacture of novel substituted aminomethanediphosphonic acids
EP1981896A2 (de)	2008-10-22	Verbessertes verfahren zur herstellung von risedronat-natrium-hemipentahydrat
EP0442378B1 (de)	1995-04-19	Selektives Verfahren für Fosinopril-Polymorphe
AU713081B2 (en)	1999-11-25	Phosphinic acid derivatives with metallopeptidase inhibitory activity
US6284909B1 (en)	2001-09-04	Preparations of thiophosphites and thiophosphonates
IL99203A (en)	1995-08-31	Process for the preparation of aminomethylphosphonic acid and aminomethylphosphinic acid
US4229383A (en)	1980-10-21	Process for the preparation of phosphoramidates