CA1304086C - Guanidine carboxylic acid esters, processes for their preparation and pharmaceutical preparations containing these compounds - Google Patents
Guanidine carboxylic acid esters, processes for their preparation and pharmaceutical preparations containing these compoundsInfo
- Publication number
- CA1304086C CA1304086C CA000560361A CA560361A CA1304086C CA 1304086 C CA1304086 C CA 1304086C CA 000560361 A CA000560361 A CA 000560361A CA 560361 A CA560361 A CA 560361A CA 1304086 C CA1304086 C CA 1304086C
- Authority
- CA
- Canada
- Prior art keywords
- group
- denotes
- propyl
- value
- methyl
- 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 - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title claims abstract description 41
- -1 Guanidine carboxylic acid esters Chemical class 0.000 title claims abstract description 29
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 title claims abstract description 23
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 title claims abstract description 16
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 230000008569 process Effects 0.000 title claims abstract description 9
- 239000000825 pharmaceutical preparation Substances 0.000 title claims abstract description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 54
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 44
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 38
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- 125000005843 halogen group Chemical group 0.000 claims description 31
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 29
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- PIQSXZSIGNOCFD-UHFFFAOYSA-N butyl n-[n-[3-(4-fluorophenyl)-3-pyridin-2-ylpropyl]-n'-[3-(1h-imidazol-5-yl)propyl]carbamimidoyl]carbamate Chemical compound C=1C=C(F)C=CC=1C(C=1N=CC=CC=1)CCN=C(NC(=O)OCCCC)NCCCC1=CNC=N1 PIQSXZSIGNOCFD-UHFFFAOYSA-N 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- OYEIMFKDCFEOOW-UHFFFAOYSA-N methyl n-[n-[3-(4-fluorophenyl)-3-pyridin-2-ylpropyl]-n'-[3-(1h-imidazol-5-yl)propyl]carbamimidoyl]carbamate Chemical compound C=1C=C(F)C=CC=1C(C=1N=CC=CC=1)CCN=C(NC(=O)OC)NCCCC1=CNC=N1 OYEIMFKDCFEOOW-UHFFFAOYSA-N 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims 3
- 150000001733 carboxylic acid esters Chemical class 0.000 claims 2
- FCHLOVOYNAFDOV-UHFFFAOYSA-N ethyl n-[n-[3-(4-fluorophenyl)-3-pyridin-2-ylpropyl]-n'-[3-(1h-imidazol-5-yl)propyl]carbamimidoyl]carbamate Chemical compound C=1C=C(F)C=CC=1C(C=1N=CC=CC=1)CCN=C(NC(=O)OCC)NCCCC1=CNC=N1 FCHLOVOYNAFDOV-UHFFFAOYSA-N 0.000 claims 1
- 150000002357 guanidines Chemical class 0.000 claims 1
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 claims 1
- DPTRIXAWYKXUCX-UHFFFAOYSA-N methyl n-[n'-[3-(1h-imidazol-5-yl)propyl]-n-(4-pyridin-2-ylbutyl)carbamimidoyl]carbamate Chemical compound C=1C=CC=NC=1CCCCN=C(NC(=O)OC)NCCCC1=CNC=N1 DPTRIXAWYKXUCX-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 6
- 239000000556 agonist Substances 0.000 abstract description 4
- 150000002148 esters Chemical class 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 74
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 27
- 125000001072 heteroaryl group Chemical group 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- 229910052801 chlorine Inorganic materials 0.000 description 25
- 229910052731 fluorine Inorganic materials 0.000 description 21
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 20
- 238000001704 evaporation Methods 0.000 description 18
- 230000008020 evaporation Effects 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 239000000460 chlorine Substances 0.000 description 17
- 239000011737 fluorine Substances 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 239000013078 crystal Substances 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 13
- 125000001309 chloro group Chemical group Cl* 0.000 description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- IHDFTEVCMVTMSP-UHFFFAOYSA-N 3-(1h-imidazol-5-yl)propan-1-amine Chemical compound NCCCC1=CN=CN1 IHDFTEVCMVTMSP-UHFFFAOYSA-N 0.000 description 11
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 229910052794 bromium Inorganic materials 0.000 description 11
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 description 8
- 239000012043 crude product Substances 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 6
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 125000005110 aryl thio group Chemical group 0.000 description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 4
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 125000003107 substituted aryl group Chemical group 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- IHJAPZIGBLPUHC-UHFFFAOYSA-N 3-(4-fluorophenyl)-3-pyridin-2-ylpropan-1-amine Chemical compound C=1C=CC=NC=1C(CCN)C1=CC=C(F)C=C1 IHJAPZIGBLPUHC-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 125000004104 aryloxy group Chemical group 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
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 210000001198 duodenum Anatomy 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229910052602 gypsum Inorganic materials 0.000 description 2
- 239000010440 gypsum Substances 0.000 description 2
- MURRAGMMNAYLNA-UHFFFAOYSA-N impromidine Chemical compound N1C=NC(CSCCNC(N)=NCCCC=2NC=NC=2)=C1C MURRAGMMNAYLNA-UHFFFAOYSA-N 0.000 description 2
- 229950005073 impromidine Drugs 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 230000009090 positive inotropic effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- COYQRJUVPRPWEO-UHFFFAOYSA-N (N-carbamoylanilino) ethyl carbonate Chemical compound C(C)OC(=O)ON(C(O)=N)C1=CC=CC=C1 COYQRJUVPRPWEO-UHFFFAOYSA-N 0.000 description 1
- KZZIVOLMJPSDEP-UHFFFAOYSA-N 1-[3-(4-fluorophenyl)-3-pyridin-2-ylpropyl]-2-[3-(1h-imidazol-5-yl)propyl]guanidine Chemical compound C=1N=CNC=1CCCN=C(N)NCCC(C=1N=CC=CC=1)C1=CC=C(F)C=C1 KZZIVOLMJPSDEP-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- PNCWHIAZZSDHPU-UHFFFAOYSA-N 2-benzylsulfanylethanamine Chemical compound NCCSCC1=CC=CC=C1 PNCWHIAZZSDHPU-UHFFFAOYSA-N 0.000 description 1
- ZLAZJIVHGNBAGG-UHFFFAOYSA-N 2-phenyl-2-pyridin-2-ylethanamine Chemical compound C=1C=CC=NC=1C(CN)C1=CC=CC=C1 ZLAZJIVHGNBAGG-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- BNCFKRVOUNWXAY-UHFFFAOYSA-N 3-(3,4-dichlorophenyl)-3-pyridin-2-ylpropan-1-amine Chemical compound C=1C=CC=NC=1C(CCN)C1=CC=C(Cl)C(Cl)=C1 BNCFKRVOUNWXAY-UHFFFAOYSA-N 0.000 description 1
- TXPCVRVMANKQKT-UHFFFAOYSA-N 3-(3,4-difluorophenyl)-3-pyridin-2-ylpropan-1-amine Chemical compound C=1C=CC=NC=1C(CCN)C1=CC=C(F)C(F)=C1 TXPCVRVMANKQKT-UHFFFAOYSA-N 0.000 description 1
- AEHWOADEGSNSBF-UHFFFAOYSA-N 3-(4-fluorophenyl)-3-phenylpropan-1-amine Chemical compound C=1C=C(F)C=CC=1C(CCN)C1=CC=CC=C1 AEHWOADEGSNSBF-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 102000003710 Histamine H2 Receptors Human genes 0.000 description 1
- 108090000050 Histamine H2 Receptors Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- HVCXNAFOVWYFHF-UHFFFAOYSA-N OC(N(CCC(C(C=C1)=CC=C1F)C1=NC=CC=C1)OC(OC1=CC=CC=C1)=O)=NC1=CC=CC=C1 Chemical compound OC(N(CCC(C(C=C1)=CC=C1F)C1=NC=CC=C1)OC(OC1=CC=CC=C1)=O)=NC1=CC=CC=C1 HVCXNAFOVWYFHF-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- JJCVQQNEWQVABW-UHFFFAOYSA-N [5-amino-4-(2-aminoethylsulfanylmethyl)-3h-1,3-thiazol-2-ylidene]methanediamine Chemical compound NCCSCC1=C(N)SC(=C(N)N)N1 JJCVQQNEWQVABW-UHFFFAOYSA-N 0.000 description 1
- FJMIORIRCVKHLE-UHFFFAOYSA-N [amino(methylsulfanyl)methylidene]-(3,3-diphenylpropyl)azanium;iodide Chemical compound [I-].C=1C=CC=CC=1C(CC[NH+]=C(N)SC)C1=CC=CC=C1 FJMIORIRCVKHLE-UHFFFAOYSA-N 0.000 description 1
- HQRKLKDDESBBQC-UHFFFAOYSA-N [amino(methylsulfanyl)methylidene]-(4-pyridin-2-ylbutyl)azanium;iodide Chemical compound [I-].CSC(N)=[NH+]CCCCC1=CC=CC=N1 HQRKLKDDESBBQC-UHFFFAOYSA-N 0.000 description 1
- WWNKNMUEIPPBIU-UHFFFAOYSA-N [amino(methylsulfanyl)methylidene]-[2-[(4-chlorophenyl)methyl-pyridin-2-ylamino]ethyl]azanium iodide Chemical compound [I-].C=1C=CC=NC=1N(CC[NH+]=C(N)SC)CC1=CC=C(Cl)C=C1 WWNKNMUEIPPBIU-UHFFFAOYSA-N 0.000 description 1
- YGWZGTIYPDHJFO-UHFFFAOYSA-N [amino(methylsulfanyl)methylidene]-[3-(4-fluorophenyl)-3-pyridin-2-ylpropyl]azanium;iodide Chemical compound [I-].C=1C=CC=NC=1C(CC[NH+]=C(N)SC)C1=CC=C(F)C=C1 YGWZGTIYPDHJFO-UHFFFAOYSA-N 0.000 description 1
- DGLSUFNMSSVIDH-UHFFFAOYSA-N [amino(methylsulfanyl)methylidene]-[3-(n-pyridin-2-ylanilino)propyl]azanium;iodide Chemical compound [I-].C=1C=CC=NC=1N(CCC[NH+]=C(N)SC)C1=CC=CC=C1 DGLSUFNMSSVIDH-UHFFFAOYSA-N 0.000 description 1
- VGFOTUWZKBZFNV-UHFFFAOYSA-N [amino(methylsulfanyl)methylidene]-[4-(pyridin-2-ylamino)butyl]azanium;iodide Chemical compound [I-].CSC(N)=[NH+]CCCCNC1=CC=CC=N1 VGFOTUWZKBZFNV-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- 210000001765 aortic valve Anatomy 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical group C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- YJVVBGVOKJWNLR-UHFFFAOYSA-N benzyl n-[n-[3-(4-fluorophenyl)-3-pyridin-2-ylpropyl]-n'-[3-(1h-imidazol-5-yl)propyl]carbamimidoyl]carbamate Chemical compound C1=CC(F)=CC=C1C(C=1N=CC=CC=1)CCN=C(NC(=O)OCC=1C=CC=CC=1)NCCCC1=CNC=N1 YJVVBGVOKJWNLR-UHFFFAOYSA-N 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000003177 cardiotonic effect Effects 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960004132 diethyl ether Drugs 0.000 description 1
- 201000011304 dilated cardiomyopathy 1A Diseases 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- PUSKHXMZPOMNTQ-UHFFFAOYSA-N ethyl 2,1,3-benzoselenadiazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=C2N=[Se]=NC2=C1 PUSKHXMZPOMNTQ-UHFFFAOYSA-N 0.000 description 1
- RKQZUCDYNYVXPH-UHFFFAOYSA-N ethyl N-(C-methylsulfanylcarbonimidoyl)-N-(4-pyridin-2-ylbutyl)carbamate Chemical compound N1=C(C=CC=C1)CCCCN(C(SC)=N)C(=O)OCC RKQZUCDYNYVXPH-UHFFFAOYSA-N 0.000 description 1
- CGTSRXDDJFGQHR-UHFFFAOYSA-N ethyl n-(diphenoxymethylidene)carbamate Chemical compound C=1C=CC=CC=1OC(=NC(=O)OCC)OC1=CC=CC=C1 CGTSRXDDJFGQHR-UHFFFAOYSA-N 0.000 description 1
- KYXQKKTUIQMUMS-UHFFFAOYSA-N ethyl n-[n'-[3-(1h-imidazol-5-yl)propyl]-n-(4-pyridin-2-ylbutyl)carbamimidoyl]carbamate Chemical compound C=1C=CC=NC=1CCCCN=C(NC(=O)OCC)NCCCC1=CNC=N1 KYXQKKTUIQMUMS-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 230000001435 haemodynamic effect Effects 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000000297 inotrophic effect Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229940057952 methanol Drugs 0.000 description 1
- YLGXILFCIXHCMC-JHGZEJCSSA-N methyl cellulose Chemical compound COC1C(OC)C(OC)C(COC)O[C@H]1O[C@H]1C(OC)C(OC)C(OC)OC1COC YLGXILFCIXHCMC-JHGZEJCSSA-N 0.000 description 1
- OPGQGYQPVOWUOO-UHFFFAOYSA-N methyl n'-[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethyl]carbamimidothioate;hydroiodide Chemical compound I.CSC(=N)NCCSCC=1N=CNC=1C OPGQGYQPVOWUOO-UHFFFAOYSA-N 0.000 description 1
- PAVDBWFMFPEZIE-UHFFFAOYSA-N methyl n-(diaminomethylidene)carbamate Chemical compound COC(=O)NC(N)=N PAVDBWFMFPEZIE-UHFFFAOYSA-N 0.000 description 1
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
- 229960002237 metoprolol Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- KCHYYPWERNLMRO-UHFFFAOYSA-N phenyl N-[N-[3-(4-fluorophenyl)-3-pyridin-2-ylpropyl]-N-[3-(1H-imidazol-5-yl)propyl]carbamimidoyl]carbamate Chemical compound N1C=NC(=C1)CCCN(C(=N)NC(=O)OC1=CC=CC=C1)CCC(C1=NC=CC=C1)C1=CC=C(C=C1)F KCHYYPWERNLMRO-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- NQLVQOSNDJXLKG-UHFFFAOYSA-N prosulfocarb Chemical compound CCCN(CCC)C(=O)SCC1=CC=CC=C1 NQLVQOSNDJXLKG-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003510 tertiary aliphatic amines Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP3726381.7 | 1987-08-07 | ||
| DE19873726381 DE3726381A1 (de) | 1987-08-07 | 1987-08-07 | Guanidincarbonsaeureester, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1304086C true CA1304086C (en) | 1992-06-23 |
Family
ID=6333331
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000560361A Expired - Lifetime CA1304086C (en) | 1987-08-07 | 1988-03-02 | Guanidine carboxylic acid esters, processes for their preparation and pharmaceutical preparations containing these compounds |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US4948802A (en, 2012) |
| EP (1) | EP0302164B1 (en, 2012) |
| JP (1) | JPS6442470A (en, 2012) |
| KR (1) | KR890003737A (en, 2012) |
| AR (1) | AR243873A1 (en, 2012) |
| AT (1) | ATE84531T1 (en, 2012) |
| AU (1) | AU599752B2 (en, 2012) |
| CA (1) | CA1304086C (en, 2012) |
| DE (2) | DE3726381A1 (en, 2012) |
| DK (1) | DK194388A (en, 2012) |
| ES (1) | ES2053595T3 (en, 2012) |
| GR (1) | GR3006790T3 (en, 2012) |
| HU (2) | HU201053B (en, 2012) |
| IE (1) | IE63297B1 (en, 2012) |
| IL (1) | IL85542A0 (en, 2012) |
| NZ (1) | NZ223684A (en, 2012) |
| PT (1) | PT87184B (en, 2012) |
| ZA (1) | ZA881271B (en, 2012) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3631334A1 (de) * | 1986-09-15 | 1988-03-17 | Heumann Pharma Gmbh & Co | Neue imidazolylguanidinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE59008807D1 (de) * | 1990-01-15 | 1995-05-04 | Heumann Pharma Gmbh & Co | Imidazolylpropylguanidinderivat, Verfahren zu seiner Herstellung und diese Verbindung enthaltende Arzneimittel. |
| USRE37303E1 (en) * | 1992-01-10 | 2001-07-31 | Institut National Del La Sante Et De La Recherche Medicale | Imidazole compounds and their therapeutic applications |
| FR2686084B1 (fr) * | 1992-01-10 | 1995-12-22 | Bioprojet Soc Civ | Nouveaux derives de l'imidazole, leur preparation et leurs applications therapeutiques. |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3968216A (en) * | 1969-10-29 | 1976-07-06 | Smith Kline & French Laboratories Limited | Method of inhibiting histamine activity with guanidine compounds |
| BE758146A (fr) * | 1969-10-29 | 1971-04-28 | Smith Kline French Lab | Derives de l'amidine |
| GB1305547A (en, 2012) * | 1969-10-29 | 1973-02-07 | ||
| DE2630847A1 (de) * | 1976-07-09 | 1978-01-19 | Bayer Ag | Methoxycarbonyl-phenyl-guanidine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| DE3512084A1 (de) * | 1985-04-02 | 1986-10-09 | Ludwig Heumann & Co GmbH, 8500 Nürnberg | Guanidinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE3528214A1 (de) * | 1985-08-06 | 1987-02-12 | Heumann Ludwig & Co Gmbh | Arylalkylguanidinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE3528215A1 (de) * | 1985-08-06 | 1987-02-12 | Heumann Ludwig & Co Gmbh | Heteroarylalkylguanidinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE3579000D1 (de) * | 1985-04-02 | 1990-09-06 | Heumann Pharma Gmbh & Co | Imidazolylalkylguanidinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel. |
| DE3631334A1 (de) * | 1986-09-15 | 1988-03-17 | Heumann Pharma Gmbh & Co | Neue imidazolylguanidinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
-
1987
- 1987-08-07 DE DE19873726381 patent/DE3726381A1/de not_active Withdrawn
-
1988
- 1988-02-18 DE DE8888102371T patent/DE3877454D1/de not_active Expired - Fee Related
- 1988-02-18 ES ES88102371T patent/ES2053595T3/es not_active Expired - Lifetime
- 1988-02-18 EP EP88102371A patent/EP0302164B1/de not_active Expired - Lifetime
- 1988-02-18 AT AT88102371T patent/ATE84531T1/de not_active IP Right Cessation
- 1988-02-24 IL IL85542A patent/IL85542A0/xx not_active IP Right Cessation
- 1988-02-24 ZA ZA881271A patent/ZA881271B/xx unknown
- 1988-02-26 AU AU12320/88A patent/AU599752B2/en not_active Ceased
- 1988-02-29 NZ NZ223684A patent/NZ223684A/xx unknown
- 1988-03-02 CA CA000560361A patent/CA1304086C/en not_active Expired - Lifetime
- 1988-04-05 AR AR88310486A patent/AR243873A1/es active
- 1988-04-07 PT PT87184A patent/PT87184B/pt not_active IP Right Cessation
- 1988-04-08 JP JP63088017A patent/JPS6442470A/ja active Pending
- 1988-04-08 DK DK194388A patent/DK194388A/da not_active Application Discontinuation
- 1988-04-08 HU HU881777A patent/HU201053B/hu not_active IP Right Cessation
- 1988-04-08 HU HU881444A patent/HUT49604A/hu unknown
- 1988-04-08 IE IE105088A patent/IE63297B1/en not_active IP Right Cessation
- 1988-04-11 US US07/180,135 patent/US4948802A/en not_active Expired - Fee Related
- 1988-04-11 KR KR1019880004088A patent/KR890003737A/ko not_active Ceased
-
1993
- 1993-01-14 GR GR930400045T patent/GR3006790T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR890003737A (ko) | 1989-04-17 |
| AU599752B2 (en) | 1990-07-26 |
| EP0302164B1 (de) | 1993-01-13 |
| ES2053595T3 (es) | 1994-08-01 |
| DE3726381A1 (de) | 1989-02-16 |
| JPS6442470A (en) | 1989-02-14 |
| GR3006790T3 (en, 2012) | 1993-06-30 |
| AU1232088A (en) | 1989-02-09 |
| IE63297B1 (en) | 1995-04-05 |
| ATE84531T1 (de) | 1993-01-15 |
| AR243873A1 (es) | 1993-09-30 |
| NZ223684A (en) | 1989-11-28 |
| EP0302164A1 (de) | 1989-02-08 |
| PT87184B (pt) | 1995-03-01 |
| PT87184A (pt) | 1989-06-30 |
| DK194388A (da) | 1989-02-08 |
| DK194388D0 (da) | 1988-04-08 |
| DE3877454D1 (de) | 1993-02-25 |
| HUT49604A (en) | 1989-10-30 |
| US4948802A (en) | 1990-08-14 |
| IL85542A0 (en) | 1988-08-31 |
| ZA881271B (en) | 1988-08-22 |
| IE881050L (en) | 1989-02-07 |
| HU201053B (en) | 1990-09-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HU198300B (en) | Process for producing 2-/n-substituted guanidino/-4-heteroaryl-triazol derivatives | |
| US6127343A (en) | Somatostatin agonists and antagonists | |
| CZ220295A3 (en) | Heterocyclylbenzoyl guanidine, process of its preparation and pharmaceutical composition containing thereof | |
| HU207945B (en) | Process for producing neuropeptide-y-antagonisticpharmaceutical compositions containing imidazolyl-alkyl-guanidine derivative | |
| US5180724A (en) | Carboxamide amino acid heterobicyclic paf antagonists | |
| CA1249829A (en) | Imidazolylguanidine derivatives, processes for their preparation and medicaments containing these compounds | |
| AU2003257300A1 (en) | Amino benzothiazole compounds with nos inhibitory activity | |
| AU715751B2 (en) | New benzimidazole, benzoxazole and benzothiazole compounds, process for preparing them and pharmaceutical compositions containing them | |
| CA1266657A (en) | Imidazolyl alkyl guanidine derivatives, processes for their preparation and pharmaceutical preparations containing these compounds | |
| CA1304086C (en) | Guanidine carboxylic acid esters, processes for their preparation and pharmaceutical preparations containing these compounds | |
| AU598636B2 (en) | Dihydropyridazinone derivatives, a process for their preparation and pharmaceutical preparations containing these compounds | |
| EP0230035B1 (en) | Omega-[(hetero)alkyl]benz[cd]indol-2-amines | |
| US5212187A (en) | Pyridyl alkylamine compounds which are useful against histamine h1 and h2 receptors | |
| CA1213279A (en) | Thiomethylpyridine derivatives, process for the production thereof and medicaments containing them | |
| US4968683A (en) | 6-oxo-pyridazine derivatives, a process for their preparation and medicaments containing these compounds | |
| CZ289922B6 (cs) | Derivát 4-aminobenzoylguanidinu, substituovaného v orto-poloze, způsob jeho přípravy a farmaceutický prostředek, který ho obsahuje | |
| JPH03291277A (ja) | アミノピリミジン誘導体、その製造方法、該誘導体を含有する心臓血管疾病を治療するための医薬組成物および中間生成物 | |
| US4738960A (en) | 1,3,4-Thiadiazole derivatives and pharmaceutical preparations useful as inhibitors for histamine-H2 receptors | |
| US5108998A (en) | Cardiotonic thiadiazine derivatives | |
| JPH0827113A (ja) | ヘテロシクリルオキシベンゾイルグアニジン | |
| NZ208056A (en) | Pyrimidine-thioalkyl-pyridines and pharmaceutical compositions | |
| US5441948A (en) | 1,3,4-benzotraizepin-5(4H)-one derivatives and process for the preparation thereof | |
| JPS5846083A (ja) | 新規な３′−置換−５′−（２−アミノ−４−ピリジル）−１′，２′，４′−トリアゾ−ル類 | |
| SK12896A3 (en) | Derivatives of 4-mercaptobenzoylguanidine, substituted at ortho-position, preparation method and pharmaceutical compositions containing them | |
| JPS61236771A (ja) | イミダゾリルアルキルグアニジン誘導体、その製法およびこれらの化合物を含有する医薬製剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKLA | Lapsed | ||
| MKLA | Lapsed |
Effective date: 19970623 |