IE47543B1 - Guanidine derivatives - Google Patents
Guanidine derivativesInfo
- Publication number
- IE47543B1 IE47543B1 IE1112/78A IE111278A IE47543B1 IE 47543 B1 IE47543 B1 IE 47543B1 IE 1112/78 A IE1112/78 A IE 1112/78A IE 111278 A IE111278 A IE 111278A IE 47543 B1 IE47543 B1 IE 47543B1
- Authority
- IE
- Ireland
- Prior art keywords
- compound
- formula
- methyl
- cyano
- addition salt
- Prior art date
Links
- 150000002357 guanidines Chemical class 0.000 title 1
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 70
- 239000002253 acid Substances 0.000 claims abstract description 52
- 238000000034 method Methods 0.000 claims abstract description 50
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 28
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 28
- 230000008569 process Effects 0.000 claims abstract description 23
- 238000002360 preparation method Methods 0.000 claims abstract description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 11
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 10
- -1 4- methyl - 5 - imidazolyl Chemical group 0.000 claims description 35
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 33
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
- 239000000203 mixture Substances 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 239000012458 free base Substances 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000003107 substituted aryl group Chemical group 0.000 claims description 5
- 239000002585 base Substances 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 3
- 230000027119 gastric acid secretion Effects 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 2
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 230000002496 gastric effect Effects 0.000 abstract description 12
- 230000028327 secretion Effects 0.000 abstract description 10
- 241001465754 Metazoa Species 0.000 abstract description 8
- 239000007858 starting material Substances 0.000 abstract description 8
- 239000005557 antagonist Substances 0.000 abstract description 4
- 102000003710 Histamine H2 Receptors Human genes 0.000 abstract description 2
- 108090000050 Histamine H2 Receptors Proteins 0.000 abstract description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 56
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 40
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- 239000000047 product Substances 0.000 description 33
- 238000006243 chemical reaction Methods 0.000 description 31
- 229960001340 histamine Drugs 0.000 description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 229960001380 cimetidine Drugs 0.000 description 21
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 21
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 20
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
- 239000000243 solution Substances 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 210000002837 heart atrium Anatomy 0.000 description 10
- 230000000694 effects Effects 0.000 description 8
- 241000282472 Canis lupus familiaris Species 0.000 description 7
- 241000700199 Cavia porcellus Species 0.000 description 7
- 238000006073 displacement reaction Methods 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 6
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 208000008469 Peptic Ulcer Diseases 0.000 description 5
- 210000004211 gastric acid Anatomy 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 210000001187 pylorus Anatomy 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 4
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- IULFXBLVJIPESI-UHFFFAOYSA-N bis(methylsulfanyl)methylidenecyanamide Chemical compound CSC(SC)=NC#N IULFXBLVJIPESI-UHFFFAOYSA-N 0.000 description 4
- 244000309464 bull Species 0.000 description 4
- YLBIBZCIFHPPKA-UHFFFAOYSA-N but-2-yn-1-amine Chemical compound CC#CCN YLBIBZCIFHPPKA-UHFFFAOYSA-N 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 239000003485 histamine H2 receptor antagonist Substances 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 4
- 208000011906 peptic ulcer disease Diseases 0.000 description 4
- 229940044551 receptor antagonist Drugs 0.000 description 4
- 239000002464 receptor antagonist Substances 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000001262 anti-secretory effect Effects 0.000 description 3
- XSBPYGDBXQXSCU-UHFFFAOYSA-N but-3-yn-1-amine Chemical compound NCCC#C XSBPYGDBXQXSCU-UHFFFAOYSA-N 0.000 description 3
- 238000004587 chromatography analysis Methods 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
- 239000012043 crude product Substances 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 description 2
- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 description 2
- VUGCBIWQHSRQBZ-UHFFFAOYSA-N 2-methylbut-3-yn-2-amine Chemical compound CC(C)(N)C#C VUGCBIWQHSRQBZ-UHFFFAOYSA-N 0.000 description 2
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 description 2
- NPYAQUAFNJHLQG-UHFFFAOYSA-N C#CCN=C(N)N(CCS)C#N Chemical compound C#CCN=C(N)N(CCS)C#N NPYAQUAFNJHLQG-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 206010065713 Gastric Fistula Diseases 0.000 description 2
- 229940122957 Histamine H2 receptor antagonist Drugs 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000001746 atrial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229940097265 cysteamine hydrochloride Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- MWSSYOOKGBJZFI-UHFFFAOYSA-N methyl n'-but-2-ynyl-n-cyanocarbamimidothioate Chemical compound N#CN=C(SC)NCC#CC MWSSYOOKGBJZFI-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000010517 secondary reaction Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- GAPFINWZKMCSBG-UHFFFAOYSA-N 2-(2-sulfanylethyl)guanidine Chemical compound NC(=N)NCCS GAPFINWZKMCSBG-UHFFFAOYSA-N 0.000 description 1
- GFNVWKLZHQYCOP-UHFFFAOYSA-N 2-but-2-ynylguanidine Chemical compound CC#CCN=C(N)N GFNVWKLZHQYCOP-UHFFFAOYSA-N 0.000 description 1
- VPLCGZRPGVDORN-UHFFFAOYSA-N 2-but-3-yn-2-ylguanidine Chemical compound CC(C#C)NC(=N)N VPLCGZRPGVDORN-UHFFFAOYSA-N 0.000 description 1
- OGDDJYMEILMUIY-UHFFFAOYSA-N 2-pent-4-ynylguanidine Chemical compound NC(=N)NCCCC#C OGDDJYMEILMUIY-UHFFFAOYSA-N 0.000 description 1
- PDWPOXKSTFGRIT-UHFFFAOYSA-N 4-(chloromethyl)-5-methyl-1h-imidazole;hydrochloride Chemical compound Cl.CC=1NC=NC=1CCl PDWPOXKSTFGRIT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- KBWQBFRMJRMRJH-UHFFFAOYSA-N CC1=C(CSCCNC(N(CCCC#C)C#N)=N)NC=N1 Chemical compound CC1=C(CSCCNC(N(CCCC#C)C#N)=N)NC=N1 KBWQBFRMJRMRJH-UHFFFAOYSA-N 0.000 description 1
- 125000006519 CCH3 Chemical group 0.000 description 1
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 238000010268 HPLC based assay Methods 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-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
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CLJHABUMMDMAFA-UHFFFAOYSA-N Nylidrin hydrochloride Chemical compound [Cl-].C=1C=C(O)C=CC=1C(O)C(C)[NH2+]C(C)CCC1=CC=CC=C1 CLJHABUMMDMAFA-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000009858 acid secretion Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- RIMGDBZXWSGBQN-UHFFFAOYSA-N burimamide Chemical compound CNC(=S)NCCCCC1=CN=C[N]1 RIMGDBZXWSGBQN-UHFFFAOYSA-N 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000002057 chronotropic effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000000938 histamine H1 antagonist Substances 0.000 description 1
- 229960004931 histamine dihydrochloride Drugs 0.000 description 1
- PPZMYIBUHIPZOS-UHFFFAOYSA-N histamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CN=CN1 PPZMYIBUHIPZOS-UHFFFAOYSA-N 0.000 description 1
- 229940077716 histamine h2 receptor antagonists for peptic ulcer and gord Drugs 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 150000002541 isothioureas Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 238000013289 male long evans rat Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- OJHSNWXCKUSASO-UHFFFAOYSA-N methyl N-cyano-N-[2-[(5-methyl-1H-imidazol-4-yl)methylsulfanyl]ethyl]carbamimidothioate Chemical compound C(#N)N(C(SC)=N)CCSCC1=C(N=CN1)C OJHSNWXCKUSASO-UHFFFAOYSA-N 0.000 description 1
- WSUNDBVVUCLXTG-UHFFFAOYSA-N methyl n-cyano-n'-[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethyl]carbamimidothioate Chemical compound N#CNC(SC)=NCCSCC=1NC=NC=1C WSUNDBVVUCLXTG-UHFFFAOYSA-N 0.000 description 1
- AOQBTOKIEVBYSK-UHFFFAOYSA-N methyl n-cyano-n'-prop-2-ynylcarbamimidothioate Chemical compound N#CNC(SC)=NCC#C AOQBTOKIEVBYSK-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- LMDDPGHBJXJGAC-UHFFFAOYSA-N pent-4-yn-1-amine Chemical compound NCCCC#C LMDDPGHBJXJGAC-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000006215 rectal suppository Substances 0.000 description 1
- 229940100618 rectal suppository Drugs 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 210000005245 right atrium Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/39—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
- C07C323/43—Y being a hetero atom
- C07C323/44—X or Y being nitrogen 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
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE2932/81A IE47544B1 (en) | 1977-06-03 | 1978-06-02 | N-cyano-n'-alkynyl-s-substituted isothioureas |
| IE2933/81A IE47545B1 (en) | 1977-06-03 | 1978-06-02 | N-cyano-n'-alkynyl-n"-(2-mercaptoethyl)-guanidines |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80300977A | 1977-06-03 | 1977-06-03 | |
| US82679677A | 1977-08-22 | 1977-08-22 | |
| US05/848,959 US4112234A (en) | 1977-08-22 | 1977-11-07 | Imidazolylmethylthioethyl alkynyl guanidines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE781112L IE781112L (en) | 1978-12-03 |
| IE47543B1 true IE47543B1 (en) | 1984-04-18 |
Family
ID=27419995
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE1112/78A IE47543B1 (en) | 1977-06-03 | 1978-06-02 | Guanidine derivatives |
Country Status (26)
| Country | Link |
|---|---|
| JP (1) | JPS543067A (el) |
| AR (2) | AR222797A1 (el) |
| CA (1) | CA1110251A (el) |
| CH (2) | CH641167A5 (el) |
| CY (3) | CY1231A (el) |
| DD (1) | DD140038A5 (el) |
| DE (1) | DE2824066A1 (el) |
| DK (1) | DK243178A (el) |
| ES (3) | ES470474A1 (el) |
| FI (1) | FI69069C (el) |
| FR (2) | FR2401143A1 (el) |
| GB (3) | GB1598629A (el) |
| GR (1) | GR73860B (el) |
| HK (3) | HK38184A (el) |
| HU (1) | HU186766B (el) |
| IE (1) | IE47543B1 (el) |
| IL (1) | IL54819A (el) |
| KE (1) | KE3373A (el) |
| LU (1) | LU79725A1 (el) |
| MY (3) | MY8500451A (el) |
| NL (1) | NL7805935A (el) |
| NO (3) | NO152214C (el) |
| NZ (1) | NZ187376A (el) |
| SE (3) | SE443784B (el) |
| SG (1) | SG8584G (el) |
| YU (4) | YU129778A (el) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS568352A (en) * | 1979-07-03 | 1981-01-28 | Shionogi & Co Ltd | Aminoalkylvenzene derivative |
| US4339439A (en) * | 1981-01-19 | 1982-07-13 | Bristol-Myers Company | Pharmaceutical methods and compositions |
| JPS57134318A (en) * | 1981-02-12 | 1982-08-19 | Nissan Motor Co Ltd | Air mixing construction of air conditioner |
| JPS5848516U (ja) * | 1981-09-30 | 1983-04-01 | 日産車体株式会社 | 車両用空気調和装置 |
| JPS6018010U (ja) * | 1983-07-18 | 1985-02-07 | 日産自動車株式会社 | 車両用空気調和装置の温度調整機構 |
| JPS60113211U (ja) * | 1984-01-06 | 1985-07-31 | 松下電器産業株式会社 | 自動車用空気調和装置 |
| ES2007948A6 (es) * | 1988-07-06 | 1989-07-01 | Vinas Lab | Procedimiento para la obtencion de derivados propargilguanidicos. |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4024271A (en) * | 1971-03-09 | 1977-05-17 | Smith Kline & French Laboratories Limited | Pharmacologically active guanidine compounds |
| GB1338169A (en) * | 1971-03-09 | 1973-11-21 | Smith Kline French Lab | Ureas thioureas and guanidines |
| GB1397436A (en) * | 1972-09-05 | 1975-06-11 | Smith Kline French Lab | Heterocyclic n-cyanoguinidines |
| GB1533380A (en) * | 1974-09-02 | 1978-11-22 | Smith Kline French Lab | Process for the preparation of heterocyclic substituted thioureas and h-cyanoguanidines |
| GB1531221A (en) * | 1974-09-02 | 1978-11-08 | Smith Kline French Lab | Process for preparing guanidine derivatives |
| GB1531231A (en) * | 1974-09-02 | 1978-11-08 | Smith Kline French Lab | Process for the production of cyanoguanidine derivatives |
-
1978
- 1978-05-25 CA CA304,045A patent/CA1110251A/en not_active Expired
- 1978-05-25 NZ NZ187376A patent/NZ187376A/xx unknown
- 1978-05-26 GB GB27637/79A patent/GB1598629A/en not_active Expired
- 1978-05-26 GB GB23611/78A patent/GB1598628A/en not_active Expired
- 1978-05-26 CY CY1231A patent/CY1231A/xx unknown
- 1978-05-26 CY CY1229A patent/CY1229A/xx unknown
- 1978-05-26 CY CY1230A patent/CY1230A/xx unknown
- 1978-05-26 GB GB18923/80A patent/GB1598630A/en not_active Expired
- 1978-05-29 LU LU79725A patent/LU79725A1/xx unknown
- 1978-05-29 GR GR56374A patent/GR73860B/el unknown
- 1978-05-31 FI FI781737A patent/FI69069C/fi not_active IP Right Cessation
- 1978-05-31 NL NL7805935A patent/NL7805935A/xx not_active Application Discontinuation
- 1978-05-31 AR AR272401A patent/AR222797A1/es active
- 1978-05-31 DK DK243178A patent/DK243178A/da not_active Application Discontinuation
- 1978-05-31 IL IL54819A patent/IL54819A/xx unknown
- 1978-05-31 YU YU01297/78A patent/YU129778A/xx unknown
- 1978-06-01 DE DE19782824066 patent/DE2824066A1/de not_active Withdrawn
- 1978-06-02 JP JP6590078A patent/JPS543067A/ja active Granted
- 1978-06-02 FR FR7816601A patent/FR2401143A1/fr active Granted
- 1978-06-02 HU HU811135A patent/HU186766B/hu unknown
- 1978-06-02 IE IE1112/78A patent/IE47543B1/en unknown
- 1978-06-02 SE SE7806525A patent/SE443784B/sv unknown
- 1978-06-02 NO NO781928A patent/NO152214C/no unknown
- 1978-06-02 ES ES470474A patent/ES470474A1/es not_active Expired
- 1978-06-02 CH CH609278A patent/CH641167A5/de not_active IP Right Cessation
- 1978-06-05 DD DD78205794A patent/DD140038A5/de unknown
-
1979
- 1979-03-01 ES ES478203A patent/ES478203A1/es not_active Expired
- 1979-03-01 ES ES478202A patent/ES478202A1/es not_active Expired
- 1979-03-05 YU YU530/79A patent/YU41620B/xx unknown
- 1979-05-16 NO NO791637A patent/NO791637L/no unknown
- 1979-10-26 AR AR278645A patent/AR222503A1/es active
- 1979-11-23 FR FR7928943A patent/FR2436138A1/fr active Granted
-
1982
- 1982-09-27 YU YU2154/82A patent/YU40624B/xx unknown
- 1982-09-27 YU YU2155/82A patent/YU40625B/xx unknown
-
1983
- 1983-09-12 NO NO833255A patent/NO151824C/no unknown
- 1983-10-07 CH CH549283A patent/CH644591A5/de not_active IP Right Cessation
-
1984
- 1984-01-30 SG SG85/84A patent/SG8584G/en unknown
- 1984-02-10 KE KE3373A patent/KE3373A/xx unknown
- 1984-03-16 SE SE8401492A patent/SE8401492D0/xx not_active Application Discontinuation
- 1984-03-16 SE SE8401491A patent/SE8401491D0/xx not_active Application Discontinuation
- 1984-05-03 HK HK381/84A patent/HK38184A/xx unknown
- 1984-05-03 HK HK380/84A patent/HK38084A/xx unknown
- 1984-05-03 HK HK382/84A patent/HK38284A/xx unknown
-
1985
- 1985-12-30 MY MY451/85A patent/MY8500451A/xx unknown
- 1985-12-30 MY MY453/85A patent/MY8500453A/xx unknown
- 1985-12-30 MY MY452/85A patent/MY8500452A/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4112234A (en) | Imidazolylmethylthioethyl alkynyl guanidines | |
| IE53274B1 (en) | Chemical compounds derived from cyclobutene | |
| JP2502343B2 (ja) | 薬学的に活性な置換ベンズアミド | |
| DD220308A5 (de) | Verfahren zur herstellung von n(piperidinylalkyl)-carboxamiden | |
| GB2088375A (en) | Imidazolylphenyl amidines | |
| KR840001075B1 (ko) | 티아졸 유도체의 제조방법 | |
| JPH0655728B2 (ja) | ヒスタミン誘導体及びその製造方法並びに該誘導体を含有する医薬 | |
| IE47543B1 (en) | Guanidine derivatives | |
| US4157347A (en) | N-cyano isothioureas | |
| KR910009213B1 (ko) | 4,5,6,7-테트라하이드로티아졸로[5,4-c]피리딘 유도체의 제조방법 | |
| US4157340A (en) | N,N'-[Bis(N-cyanoguanyl)]cystamine derivatives | |
| KR0139201B1 (ko) | 아미노벤젠술폰산 유도체 | |
| KR860000851B1 (ko) | N-(2-(((5-(디메틸아미노)-메틸-2-푸라닐)-메틸)-티오)-에틸)-n'-(3,4-메틸렌-디옥시벤질)-2-니트로-1,1-에텐디아민의 제조방법 | |
| US4200760A (en) | Imidazolylalkylthioalkylamino-ethylene derivatives | |
| USRE31588E (en) | Imidazolylmethylthioethyl alkynyl guanidines | |
| CA1142544A (en) | N-cyano-n'-(2-[(4-methyl-5-imidazolyl) methylthio]ethyl) - n"-alkynylguanidines h.sub.2 receptor blocking agents | |
| KR810000632B1 (ko) | 히스타민 h₂수용기 길항제 또는 비독성인 그의 약조제 가능한 산 첨가염의 제조방법 | |
| CA1130306A (en) | N-cyano-n'-[2-[(4-methyl-5-imidazolyl) methylthio]ethyl]- n"-alkynylguanidines h.sub.2 receptor blocking agents | |
| EP0180500A1 (fr) | Dérivés de thiéno et furo - [2,3-c]pyrroles, procédés de préparation et médicaments les contenant | |
| US5322846A (en) | 4-methylthiazole derivatives, their methods of preparation and the pharmaceutical compositions in which they are present | |
| US4221737A (en) | 1-(Alkynyl)amino-1-(mercaptoalkyl)amino ethylenes | |
| JPS63270663A (ja) | ピリジルアルキルアミンのアルキルカルボキシアミド類、その製造及び医薬組成物 | |
| KR820001614B1 (ko) | N-펜에틸 아세트아미드 화합물의 제조방법 | |
| KR800000411B1 (ko) | 퀴나졸린 유도체의 제조방법 | |
| JPS61221189A (ja) | 縮合２‐置換チアゾール誘導体 |