CA1298836C - Imidazoquinoline antithrombogenic cardiotonic agents - Google Patents
Imidazoquinoline antithrombogenic cardiotonic agentsInfo
- Publication number
- CA1298836C CA1298836C CA000505136A CA505136A CA1298836C CA 1298836 C CA1298836 C CA 1298836C CA 000505136 A CA000505136 A CA 000505136A CA 505136 A CA505136 A CA 505136A CA 1298836 C CA1298836 C CA 1298836C
- Authority
- CA
- Canada
- Prior art keywords
- compound
- imidazo
- quinolin
- formula
- dihydro
- 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 - Fee Related
Links
- 239000000496 cardiotonic agent Substances 0.000 title abstract description 5
- 230000002965 anti-thrombogenic effect Effects 0.000 title description 2
- SQQXRXKYTKFFSM-UHFFFAOYSA-N chembl1992147 Chemical compound OC1=C(OC)C(OC)=CC=C1C1=C(C)C(C(O)=O)=NC(C=2N=C3C4=NC(C)(C)N=C4C(OC)=C(O)C3=CC=2)=C1N SQQXRXKYTKFFSM-UHFFFAOYSA-N 0.000 title 1
- 229940124669 imidazoquinoline Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 122
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 59
- 239000001257 hydrogen Substances 0.000 claims abstract description 58
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 54
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 44
- 150000002367 halogens Chemical class 0.000 claims abstract description 44
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 38
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 33
- 210000001772 blood platelet Anatomy 0.000 claims abstract description 24
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims description 79
- -1 thio compound Chemical class 0.000 claims description 60
- 150000003839 salts Chemical class 0.000 claims description 41
- 239000000463 material Substances 0.000 claims description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 19
- 229940091173 hydantoin Drugs 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 150000001469 hydantoins Chemical class 0.000 claims description 12
- 230000002829 reductive effect Effects 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims description 9
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims description 9
- 230000000297 inotrophic effect Effects 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 6
- 230000001590 oxidative effect Effects 0.000 claims description 6
- 229910019142 PO4 Inorganic materials 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 5
- 239000010452 phosphate Substances 0.000 claims description 5
- ODCKPUDNMNCWMR-UHFFFAOYSA-N 7,8-dimethyl-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=C(C)C(C)=CC=C21 ODCKPUDNMNCWMR-UHFFFAOYSA-N 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- 230000002152 alkylating effect Effects 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 4
- YCKKLLYMMVHPIG-UHFFFAOYSA-N 7,8-dimethyl-1,4,9,9a-tetrahydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2CC2=C(C)C(C)=CC=C21 YCKKLLYMMVHPIG-UHFFFAOYSA-N 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
- CTZIRIUSNWPEKZ-UHFFFAOYSA-N 7-bromo-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(Br)=CC=C21 CTZIRIUSNWPEKZ-UHFFFAOYSA-N 0.000 claims description 2
- GYPSSORWUVEFFW-UHFFFAOYSA-N 7-chloro-6,8-dimethyl-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C1=C2C(C)=C(Cl)C(C)=CC2=NC2=C1NC(=O)N2 GYPSSORWUVEFFW-UHFFFAOYSA-N 0.000 claims description 2
- KOPBXGWUOMDXIW-UHFFFAOYSA-N 7-chloro-6-methyl-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C1=C2C=C(Cl)C(C)=CC2=NC2=C1NC(=O)N2 KOPBXGWUOMDXIW-UHFFFAOYSA-N 0.000 claims description 2
- WPNOABJRAVXWKU-UHFFFAOYSA-N 7-methoxy-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(OC)=CC=C21 WPNOABJRAVXWKU-UHFFFAOYSA-N 0.000 claims description 2
- VZXBGYRONYENIL-UHFFFAOYSA-N 8-chloro-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C1=C2C(Cl)=CC=CC2=NC2=C1NC(=O)N2 VZXBGYRONYENIL-UHFFFAOYSA-N 0.000 claims description 2
- YRQWFYMTPBNERX-UHFFFAOYSA-N 8-chloro-7-methyl-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=C(Cl)C(C)=CC=C21 YRQWFYMTPBNERX-UHFFFAOYSA-N 0.000 claims description 2
- VEOPPKJMCCZWDL-UHFFFAOYSA-N 8-methyl-1,4,9,9a-tetrahydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2CC2=C1C=CC=C2C VEOPPKJMCCZWDL-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- PJRUEHQERHHYKI-UHFFFAOYSA-N 1,7,8-trimethyl-3h-imidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)N(C)C2=CC2=C(C)C(C)=CC=C21 PJRUEHQERHHYKI-UHFFFAOYSA-N 0.000 claims 1
- OGGMUYJRABMJGV-UHFFFAOYSA-N 1,7-dimethyl-3h-imidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)N(C)C2=CC2=CC(C)=CC=C21 OGGMUYJRABMJGV-UHFFFAOYSA-N 0.000 claims 1
- YEZYOQWGSQOGIH-UHFFFAOYSA-N 1,8-dimethyl-3h-imidazo[4,5-b]quinolin-2-one Chemical compound C1=C2C(C)=CC=CC2=NC2=C1N(C)C(=O)N2 YEZYOQWGSQOGIH-UHFFFAOYSA-N 0.000 claims 1
- SWFQYDVZFIVQHW-UHFFFAOYSA-N 1,8-dimethyl-9,9a-dihydro-4h-imidazo[4,5-b]quinolin-2-one Chemical compound C1C2=C(C)C=CC=C2N=C2C1N(C)C(=O)N2 SWFQYDVZFIVQHW-UHFFFAOYSA-N 0.000 claims 1
- AMQUYLNSYUJEKH-UHFFFAOYSA-N 6,7,8-trimethoxy-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C1=C2C(OC)=C(OC)C(OC)=CC2=NC2=C1NC(=O)N2 AMQUYLNSYUJEKH-UHFFFAOYSA-N 0.000 claims 1
- CKJZPMFALWTSJS-UHFFFAOYSA-N 6,7-dimethoxy-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2C=C(OC)C(OC)=CC2=CC2=C1NC(=O)N2 CKJZPMFALWTSJS-UHFFFAOYSA-N 0.000 claims 1
- VBQVHGPNYUAGFI-UHFFFAOYSA-N 6,7-dimethyl-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2C=C(C)C(C)=CC2=CC2=C1NC(=O)N2 VBQVHGPNYUAGFI-UHFFFAOYSA-N 0.000 claims 1
- OIKKOZDXQORKSP-UHFFFAOYSA-N 6-(trifluoromethyl)-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C1=C2NC(=O)NC2=NC2=CC(C(F)(F)F)=CC=C21 OIKKOZDXQORKSP-UHFFFAOYSA-N 0.000 claims 1
- YEBXOZQMALFMCP-UHFFFAOYSA-N 7-bromo-6,8-dimethyl-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C1=C2C(C)=C(Br)C(C)=CC2=NC2=C1NC(=O)N2 YEBXOZQMALFMCP-UHFFFAOYSA-N 0.000 claims 1
- OSBMKBWTTUTUMA-UHFFFAOYSA-N 7-chloro-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(Cl)=CC=C21 OSBMKBWTTUTUMA-UHFFFAOYSA-N 0.000 claims 1
- SBMFEGWRZYIWGG-UHFFFAOYSA-N 7-ethoxy-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCC)=CC=C21 SBMFEGWRZYIWGG-UHFFFAOYSA-N 0.000 claims 1
- XTXHKKBSLRGOJD-UHFFFAOYSA-N 7-fluoro-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(F)=CC=C21 XTXHKKBSLRGOJD-UHFFFAOYSA-N 0.000 claims 1
- RXZNLEUDXVTIQC-UHFFFAOYSA-N 7-methoxy-1-methyl-3h-imidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)N(C)C2=CC2=CC(OC)=CC=C21 RXZNLEUDXVTIQC-UHFFFAOYSA-N 0.000 claims 1
- BSAKVJKPJIQKNP-UHFFFAOYSA-N 7-methyl-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(C)=CC=C21 BSAKVJKPJIQKNP-UHFFFAOYSA-N 0.000 claims 1
- FPYRERVDZQWRBO-UHFFFAOYSA-N 7-propan-2-yloxy-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(OC(C)C)=CC=C21 FPYRERVDZQWRBO-UHFFFAOYSA-N 0.000 claims 1
- GMKORAPPNLPTAX-UHFFFAOYSA-N 8-methoxy-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C1=C2C(OC)=CC=CC2=NC2=C1NC(=O)N2 GMKORAPPNLPTAX-UHFFFAOYSA-N 0.000 claims 1
- NFWDGDAZJTYAHA-UHFFFAOYSA-N 8-methyl-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C1=C2C(C)=CC=CC2=NC2=C1NC(=O)N2 NFWDGDAZJTYAHA-UHFFFAOYSA-N 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 123
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 95
- 229910001868 water Inorganic materials 0.000 description 94
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 85
- 239000000203 mixture Substances 0.000 description 72
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 71
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 58
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 52
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- 239000007787 solid Substances 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 34
- 239000000460 chlorine Substances 0.000 description 34
- 239000002904 solvent Substances 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 125000003118 aryl group Chemical group 0.000 description 33
- 239000000543 intermediate Substances 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 26
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 26
- 238000010992 reflux Methods 0.000 description 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
- 229910052740 iodine Inorganic materials 0.000 description 18
- 239000011630 iodine Substances 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 15
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 13
- 229910000029 sodium carbonate Inorganic materials 0.000 description 13
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 238000009835 boiling Methods 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 12
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 12
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- 229960000583 acetic acid Drugs 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 235000011167 hydrochloric acid Nutrition 0.000 description 9
- 229960000443 hydrochloric acid Drugs 0.000 description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- 239000002585 base Substances 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 8
- 229940001474 sodium thiosulfate Drugs 0.000 description 8
- 235000019345 sodium thiosulphate Nutrition 0.000 description 8
- 230000003595 spectral effect Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 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 6
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 6
- 210000004623 platelet-rich plasma Anatomy 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- LBUJPTNKIBCYBY-UHFFFAOYSA-N tetrahydroquinoline Natural products C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 6
- 102000008186 Collagen Human genes 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 239000000538 analytical sample Substances 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- KVYKDNGUEZRPGJ-UHFFFAOYSA-N 1-Aminohydantoin Chemical compound NN1CC(=O)NC1=O KVYKDNGUEZRPGJ-UHFFFAOYSA-N 0.000 description 4
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 4
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 4
- 210000002837 heart atrium Anatomy 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- FGFRGLZXPZOXAI-UHFFFAOYSA-N (2,3-dimethyl-6-nitrophenyl)methanamine Chemical compound CC1=CC=C([N+]([O-])=O)C(CN)=C1C FGFRGLZXPZOXAI-UHFFFAOYSA-N 0.000 description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 3
- JLADTIPBYWSGLM-UHFFFAOYSA-N 1-nitroimidazolidine-2,4-dione Chemical compound [O-][N+](=O)N1CC(=O)NC1=O JLADTIPBYWSGLM-UHFFFAOYSA-N 0.000 description 3
- AGIWNONRDJEVHH-UHFFFAOYSA-N 2,3-dimethyl-6-nitrobenzaldehyde Chemical compound CC1=CC=C([N+]([O-])=O)C(C=O)=C1C AGIWNONRDJEVHH-UHFFFAOYSA-N 0.000 description 3
- GYDRDYBWCJBHKC-UHFFFAOYSA-N 5-[(2-chloro-6-nitrophenyl)methyl]imidazolidine-2,4-dione Chemical compound [O-][N+](=O)C1=CC=CC(Cl)=C1CC1C(=O)NC(=O)N1 GYDRDYBWCJBHKC-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
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 239000003456 ion exchange resin Substances 0.000 description 3
- 229920003303 ion-exchange polymer Polymers 0.000 description 3
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- NYNBIZMIFBGAJF-UHFFFAOYSA-N (2,5-dioxoimidazolidin-4-yl)phosphonic acid Chemical compound OP(O)(=O)C1NC(=O)NC1=O NYNBIZMIFBGAJF-UHFFFAOYSA-N 0.000 description 2
- VSAMIQWGGAXXIK-UHFFFAOYSA-N 2-amino-3-(2,3-dimethyl-6-nitrophenyl)propanoic acid;hydrochloride Chemical compound Cl.CC1=CC=C([N+]([O-])=O)C(CC(N)C(O)=O)=C1C VSAMIQWGGAXXIK-UHFFFAOYSA-N 0.000 description 2
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 2
- 102000001707 3',5'-Cyclic-AMP Phosphodiesterases Human genes 0.000 description 2
- 108010054479 3',5'-Cyclic-AMP Phosphodiesterases Proteins 0.000 description 2
- VRGANZDDOSHADO-UHFFFAOYSA-N 3-(chloromethyl)-1,2-dimethyl-4-nitrobenzene Chemical compound CC1=CC=C([N+]([O-])=O)C(CCl)=C1C VRGANZDDOSHADO-UHFFFAOYSA-N 0.000 description 2
- VERWATQGJOEFMQ-UHFFFAOYSA-N 4-chloro-2-(chloromethyl)-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1CCl VERWATQGJOEFMQ-UHFFFAOYSA-N 0.000 description 2
- XHSCTCAIAUBTGK-UHFFFAOYSA-N 5-[(2,3-dimethyl-6-nitrophenyl)methylidene]imidazolidine-2,4-dione Chemical compound CC1=CC=C([N+]([O-])=O)C(C=C2C(NC(=O)N2)=O)=C1C XHSCTCAIAUBTGK-UHFFFAOYSA-N 0.000 description 2
- BNTDDWPHSMILHQ-UHFFFAOYSA-N 5-methoxy-2-nitrobenzaldehyde Chemical compound COC1=CC=C([N+]([O-])=O)C(C=O)=C1 BNTDDWPHSMILHQ-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000282339 Mustela Species 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- OTBXOEAOVRKTNQ-UHFFFAOYSA-N anagrelide Chemical compound N1=C2NC(=O)CN2CC2=C(Cl)C(Cl)=CC=C21 OTBXOEAOVRKTNQ-UHFFFAOYSA-N 0.000 description 2
- 229960001694 anagrelide Drugs 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical class O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000003177 cardiotonic effect Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- ISOLMABRZPQKOV-UHFFFAOYSA-N diethyl 2-acetamidopropanedioate Chemical compound CCOC(=O)C(NC(C)=O)C(=O)OCC ISOLMABRZPQKOV-UHFFFAOYSA-N 0.000 description 2
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 2
- 229960002768 dipyridamole Drugs 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical class [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 2
- 229960003574 milrinone Drugs 0.000 description 2
- PZRHRDRVRGEVNW-UHFFFAOYSA-N milrinone Chemical compound N1C(=O)C(C#N)=CC(C=2C=CN=CC=2)=C1C PZRHRDRVRGEVNW-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000009090 positive inotropic effect Effects 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 229940048910 thiosulfate Drugs 0.000 description 2
- DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- HBZVGKAFFVCHLO-UHFFFAOYSA-N (2,3-dimethyl-6-nitrophenyl)methanol Chemical compound CC1=CC=C([N+]([O-])=O)C(CO)=C1C HBZVGKAFFVCHLO-UHFFFAOYSA-N 0.000 description 1
- RSRLEAGQLHAZEZ-UHFFFAOYSA-N (3-methyl-2,5-dioxoimidazolidin-4-yl)phosphonic acid Chemical compound CN1C(C(=O)NC1=O)P(=O)(O)O RSRLEAGQLHAZEZ-UHFFFAOYSA-N 0.000 description 1
- BINWKEIURMBREF-UHFFFAOYSA-N 1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical class C1=CC=C2N=C(NC(=O)N3)C3=CC2=C1 BINWKEIURMBREF-UHFFFAOYSA-N 0.000 description 1
- KVVGGYBLPPGNMA-UHFFFAOYSA-N 1,4,9,9a-tetrahydroimidazo[4,5-b]quinolin-2-one Chemical compound C1C2=CC=CC=C2N=C2C1NC(=O)N2 KVVGGYBLPPGNMA-UHFFFAOYSA-N 0.000 description 1
- UEKFEYNZISYRRH-UHFFFAOYSA-N 1-(bromomethyl)-4,5-dimethoxy-2-nitrobenzene Chemical compound COC1=CC(CBr)=C([N+]([O-])=O)C=C1OC UEKFEYNZISYRRH-UHFFFAOYSA-N 0.000 description 1
- ZHWBLHRFLUEYEH-UHFFFAOYSA-N 1-(chloromethyl)-4,5-dimethyl-2-nitrobenzene Chemical compound CC1=CC(CCl)=C([N+]([O-])=O)C=C1C ZHWBLHRFLUEYEH-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- YEFYPFWBLCARLC-UHFFFAOYSA-N 2,3-dimethyl-6-nitroaniline Chemical compound CC1=CC=C([N+]([O-])=O)C(N)=C1C YEFYPFWBLCARLC-UHFFFAOYSA-N 0.000 description 1
- YRIHDNDJIUJPHH-UHFFFAOYSA-N 2,3-dimethyl-6-nitrobenzonitrile Chemical compound CC1=CC=C([N+]([O-])=O)C(C#N)=C1C YRIHDNDJIUJPHH-UHFFFAOYSA-N 0.000 description 1
- SLTHATJXYPMPML-UHFFFAOYSA-N 2,5-dioxoimidazolidine-4-carboxylic acid Chemical compound OC(=O)C1NC(=O)NC1=O SLTHATJXYPMPML-UHFFFAOYSA-N 0.000 description 1
- QWZQICKUZAGVFN-UHFFFAOYSA-N 2-(bromomethyl)-1-methoxy-3-nitrobenzene Chemical compound COC1=CC=CC([N+]([O-])=O)=C1CBr QWZQICKUZAGVFN-UHFFFAOYSA-N 0.000 description 1
- DVKCGPZVBQLDED-UHFFFAOYSA-N 2-(carbamoylamino)-3-(2,3-dimethyl-6-nitrophenyl)propanoic acid Chemical compound CC1=CC=C([N+]([O-])=O)C(CC(NC(N)=O)C(O)=O)=C1C DVKCGPZVBQLDED-UHFFFAOYSA-N 0.000 description 1
- DOZPYPHOCKANDD-UHFFFAOYSA-N 2-(carbamoylamino)-3-(2-chloro-6-nitrophenyl)propanoic acid Chemical compound NC(=O)NC(C(O)=O)CC1=C(Cl)C=CC=C1[N+]([O-])=O DOZPYPHOCKANDD-UHFFFAOYSA-N 0.000 description 1
- MNCBNKPLHKEZOG-UHFFFAOYSA-N 2-(chloromethyl)-1-methyl-3-nitrobenzene Chemical compound CC1=CC=CC([N+]([O-])=O)=C1CCl MNCBNKPLHKEZOG-UHFFFAOYSA-N 0.000 description 1
- RRDMOQVRYCINEH-UHFFFAOYSA-N 2-(chloromethyl)-4-fluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1CCl RRDMOQVRYCINEH-UHFFFAOYSA-N 0.000 description 1
- BWPZDLVOJNBEKI-UHFFFAOYSA-N 2-(chloromethyl)-4-methyl-1-nitrobenzene Chemical compound CC1=CC=C([N+]([O-])=O)C(CCl)=C1 BWPZDLVOJNBEKI-UHFFFAOYSA-N 0.000 description 1
- ZHBWGYHBHAJMFI-UHFFFAOYSA-N 2-acetamido-2-[3-(2-nitrophenyl)pentan-3-yl]propanedioic acid Chemical compound CCC(CC)(C1=CC=CC=C1[N+](=O)[O-])C(C(=O)O)(C(=O)O)NC(=O)C ZHBWGYHBHAJMFI-UHFFFAOYSA-N 0.000 description 1
- BFQMZFLNXTUAPT-UHFFFAOYSA-N 2-amino-3-(2,3-dimethyl-6-nitrophenyl)propanoic acid;hydrate;hydrochloride Chemical compound O.Cl.CC1=CC=C([N+]([O-])=O)C(CC(N)C(O)=O)=C1C BFQMZFLNXTUAPT-UHFFFAOYSA-N 0.000 description 1
- JAEJSNFTJMYIEF-UHFFFAOYSA-N 2-benzylpropanedioic acid Chemical class OC(=O)C(C(O)=O)CC1=CC=CC=C1 JAEJSNFTJMYIEF-UHFFFAOYSA-N 0.000 description 1
- HJLVYZHBPDCSID-UHFFFAOYSA-N 2-chloro-4-(chloromethyl)-1,3-dimethyl-5-nitrobenzene Chemical compound CC1=CC([N+]([O-])=O)=C(CCl)C(C)=C1Cl HJLVYZHBPDCSID-UHFFFAOYSA-N 0.000 description 1
- LBHWNZFYCKTRFN-UHFFFAOYSA-N 2-methyl-6-nitrobenzaldehyde Chemical compound CC1=CC=CC([N+]([O-])=O)=C1C=O LBHWNZFYCKTRFN-UHFFFAOYSA-N 0.000 description 1
- FHHWJBYTBSEZHE-UHFFFAOYSA-N 2-methylsulfanyl-6-(trifluoromethyl)-1h-imidazo[4,5-b]quinoline Chemical compound FC(F)(F)C1=CC=C2C=C(NC(SC)=N3)C3=NC2=C1 FHHWJBYTBSEZHE-UHFFFAOYSA-N 0.000 description 1
- FSBZIYRDBQTBCB-UHFFFAOYSA-N 3-(bromomethyl)-2-chloro-1-methyl-4-nitrobenzene Chemical compound CC1=CC=C([N+]([O-])=O)C(CBr)=C1Cl FSBZIYRDBQTBCB-UHFFFAOYSA-N 0.000 description 1
- VIUDTWATMPPKEL-UHFFFAOYSA-N 3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1 VIUDTWATMPPKEL-UHFFFAOYSA-N 0.000 description 1
- PRWHHVWBMYEGBG-UHFFFAOYSA-N 4-(bromomethyl)-2-chloro-1,3-dimethyl-5-nitrobenzene Chemical compound CC1=CC([N+]([O-])=O)=C(CBr)C(C)=C1Cl PRWHHVWBMYEGBG-UHFFFAOYSA-N 0.000 description 1
- BJTZEZQMKQITAS-UHFFFAOYSA-N 5,5a,6,10-tetrahydro-3h-imidazo[2,1-b]quinazolin-2-one Chemical class C1C=CC=C2NC3=NC(=O)CN3CC21 BJTZEZQMKQITAS-UHFFFAOYSA-N 0.000 description 1
- YKTRUMDBBHMCIM-UHFFFAOYSA-N 5-[(2,3-dimethyl-6-nitrophenyl)methyl]imidazolidine-2,4-dione Chemical compound CC1=CC=C([N+]([O-])=O)C(CC2C(NC(=O)N2)=O)=C1C YKTRUMDBBHMCIM-UHFFFAOYSA-N 0.000 description 1
- HOEUDOHXWFWZPR-UHFFFAOYSA-N 5-[(2-methoxy-6-nitrophenyl)methyl]imidazolidine-2,4-dione Chemical compound COC1=CC=CC([N+]([O-])=O)=C1CC1C(=O)NC(=O)N1 HOEUDOHXWFWZPR-UHFFFAOYSA-N 0.000 description 1
- UHBKAIMRBMARAT-UHFFFAOYSA-N 5-[(4,5-dimethyl-2-nitrophenyl)methyl]imidazolidine-2,4-dione Chemical compound C1=C(C)C(C)=CC(CC2C(NC(=O)N2)=O)=C1[N+]([O-])=O UHBKAIMRBMARAT-UHFFFAOYSA-N 0.000 description 1
- RYQMWRNCEHFJKV-UHFFFAOYSA-N 5-[(5-chloro-2-nitrophenyl)methyl]imidazolidine-2,4-dione Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1CC1C(=O)NC(=O)N1 RYQMWRNCEHFJKV-UHFFFAOYSA-N 0.000 description 1
- BFEWKTVDFKGUJP-UHFFFAOYSA-N 5-[(5-ethoxy-2-nitrophenyl)methylidene]imidazolidine-2,4-dione Chemical compound CCOC1=CC=C([N+]([O-])=O)C(C=C2C(NC(=O)N2)=O)=C1 BFEWKTVDFKGUJP-UHFFFAOYSA-N 0.000 description 1
- KXIFFDHDTNVQPJ-UHFFFAOYSA-N 5-diethoxyphosphoryl-1-methylimidazolidine-2,4-dione Chemical compound CCOP(=O)(OCC)C1N(C)C(=O)NC1=O KXIFFDHDTNVQPJ-UHFFFAOYSA-N 0.000 description 1
- PNQYQNIOVAYJJG-UHFFFAOYSA-N 5-diethoxyphosphorylimidazolidine-2,4-dione Chemical compound CCOP(=O)(OCC)C1NC(=O)NC1=O PNQYQNIOVAYJJG-UHFFFAOYSA-N 0.000 description 1
- IJQHZBDBXANCIL-UHFFFAOYSA-N 5-ethoxy-2-nitrobenzaldehyde Chemical compound CCOC1=CC=C([N+]([O-])=O)C(C=O)=C1 IJQHZBDBXANCIL-UHFFFAOYSA-N 0.000 description 1
- PBNUPOARCGPMPA-UHFFFAOYSA-N 5-hydroxy-1,2-dimethyl-4,6-dinitro-3-indolecarboxylic acid ethyl ester Chemical compound [O-][N+](=O)C1=C(O)C([N+]([O-])=O)=C2C(C(=O)OCC)=C(C)N(C)C2=C1 PBNUPOARCGPMPA-UHFFFAOYSA-N 0.000 description 1
- RRIHLKALTPUKMT-UHFFFAOYSA-N 6-(trifluoromethyl)-1,3-dihydroimidazo[4,5-b]quinoline-2-thione Chemical compound C1=C2NC(=S)NC2=NC2=CC(C(F)(F)F)=CC=C21 RRIHLKALTPUKMT-UHFFFAOYSA-N 0.000 description 1
- YCSZUPKAYHUDPV-UHFFFAOYSA-N 6-amino-2,3-dimethylbenzaldehyde Chemical group CC1=CC=C(N)C(C=O)=C1C YCSZUPKAYHUDPV-UHFFFAOYSA-N 0.000 description 1
- AEOBEOJCBAYXBA-UHFFFAOYSA-N A2P5P Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1OP(O)(O)=O AEOBEOJCBAYXBA-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 101100495531 Caenorhabditis elegans cgh-1 gene Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010008132 Cerebral thrombosis Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 241000196224 Codium Species 0.000 description 1
- 206010011091 Coronary artery thrombosis Diseases 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- 241000448280 Elates Species 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000212342 Sium Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241001061127 Thione Species 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 230000002744 anti-aggregatory effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000002001 anti-metastasis Effects 0.000 description 1
- 229940053195 antiepileptics hydantoin derivative Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940095076 benzaldehyde Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 150000005524 benzylchlorides Chemical class 0.000 description 1
- 125000001743 benzylic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000000168 bronchodilator agent Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000002327 cardiovascular agent Substances 0.000 description 1
- 229940125692 cardiovascular agent Drugs 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000002057 chronotropic effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 208000002528 coronary thrombosis Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 229940095074 cyclic amp Drugs 0.000 description 1
- IPWQOZCSQLTKOI-QMMMGPOBSA-N d-[(amino)carbonyl]phenylalanine Chemical compound NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 IPWQOZCSQLTKOI-QMMMGPOBSA-N 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- YDVNLQGCLLPHAH-UHFFFAOYSA-N dichloromethane;hydrate Chemical compound O.ClCCl YDVNLQGCLLPHAH-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- VJECBOKJABCYMF-UHFFFAOYSA-N doxazosin mesylate Chemical compound [H+].CS([O-])(=O)=O.C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 VJECBOKJABCYMF-UHFFFAOYSA-N 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- WGFZASSLNBYRBE-UHFFFAOYSA-N ethoxy-[2-[2-[2-[ethoxy(hydroxy)phosphoryl]phenoxy]ethoxy]phenyl]phosphinic acid Chemical compound CCOP(O)(=O)C1=CC=CC=C1OCCOC1=CC=CC=C1P(O)(=O)OCC WGFZASSLNBYRBE-UHFFFAOYSA-N 0.000 description 1
- GSHIMLJYRQARFW-UHFFFAOYSA-N ethyl 4-[(5-chloro-4-methyl-2-nitrophenyl)methyl]-2,5-dioxoimidazolidine-4-carboxylate Chemical compound C=1C(Cl)=C(C)C=C([N+]([O-])=O)C=1CC1(C(=O)OCC)NC(=O)NC1=O GSHIMLJYRQARFW-UHFFFAOYSA-N 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 210000001308 heart ventricle Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid group Chemical group C(CCCCCC)(=O)O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000004041 inotropic agent Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000005649 metathesis reaction Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- VZXMZMJSGLFKQI-ABVWVHJUSA-N midafotel Chemical compound OC(=O)[C@H]1CN(C\C=C\P(O)(O)=O)CCN1 VZXMZMJSGLFKQI-ABVWVHJUSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000004712 monophosphates Chemical class 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- OWMJAQBUFVTERI-UHFFFAOYSA-N n-(2-formylphenyl)acetamide Chemical compound CC(=O)NC1=CC=CC=C1C=O OWMJAQBUFVTERI-UHFFFAOYSA-N 0.000 description 1
- FPTSHGHJRDQREH-UHFFFAOYSA-N n-[2-[(2,5-dioxoimidazolidin-4-yl)methyl]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1CC1C(=O)NC(=O)N1 FPTSHGHJRDQREH-UHFFFAOYSA-N 0.000 description 1
- SMEPJYZNEGJTLK-UHFFFAOYSA-N n-[4-bromo-2-[(2,5-dioxoimidazolidin-4-yl)methyl]phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(Br)C=C1CC1C(=O)NC(=O)N1 SMEPJYZNEGJTLK-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum 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
- 210000000056 organ Anatomy 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 230000032696 parturition Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 230000008288 physiological mechanism Effects 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000001210 retinal vessel Anatomy 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000003998 snake venom Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Substances [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 1
- RBWSWDPRDBEWCR-RKJRWTFHSA-N sodium;(2r)-2-[(2r)-3,4-dihydroxy-5-oxo-2h-furan-2-yl]-2-hydroxyethanolate Chemical compound [Na+].[O-]C[C@@H](O)[C@H]1OC(=O)C(O)=C1O RBWSWDPRDBEWCR-RKJRWTFHSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 201000005060 thrombophlebitis Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US72686985A | 1985-04-25 | 1985-04-25 | |
| US726,869 | 1985-04-25 | ||
| US06/832,212 US4668686A (en) | 1985-04-25 | 1986-02-26 | Imidazoquinoline antithrombrogenic cardiotonic agents |
| US832,212 | 1986-02-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1298836C true CA1298836C (en) | 1992-04-14 |
Family
ID=27111398
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000505136A Expired - Fee Related CA1298836C (en) | 1985-04-25 | 1986-03-26 | Imidazoquinoline antithrombogenic cardiotonic agents |
Country Status (32)
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4775674A (en) * | 1986-05-23 | 1988-10-04 | Bristol-Myers Company | Imidazoquinolinylether derivatives useful as phosphodiesterase and blood aggregation inhibitors |
| US4701459A (en) * | 1986-07-08 | 1987-10-20 | Bristol-Myers Company | 7-amino-1,3-dihydro-2H-imidazo[4,5-b]quinolin 2-ones and method for inhibiting phosphodiesterase and blood platelet aggregation |
| US4803210A (en) * | 1987-05-29 | 1989-02-07 | Merrell Dow Pharmaceuticals Inc. | Cardiotonic tricyclic oxazolones |
| US4743607A (en) * | 1987-05-29 | 1988-05-10 | Merrell Dow Pharmaceuticals Inc. | Cardiotonic tricyclic imidazolones |
| US4943573A (en) * | 1989-11-01 | 1990-07-24 | Bristol-Myers Squibb Company | Imidazo[4,5-b]quinolinyloxyalkanoic acid amides with enhanced water solubility |
| DE4035854C2 (de) * | 1990-11-10 | 1996-10-02 | Daimler Benz Ag | Vorrichtung zum Fangen und Ableiten des von einem Fahrzeugrad hochgeschleuderten Spritzwassers |
| PH31245A (en) * | 1991-10-30 | 1998-06-18 | Janssen Pharmaceutica Nv | 1,3-Dihydro-2H-imidazoÄ4,5-BÜ-quinolin-2-one derivatives. |
| US5196428A (en) * | 1992-04-03 | 1993-03-23 | Bristol-Myers Squibb Company | Imidazo[4,5-b]qinolinyl oxy alkyl ureas |
| US5208237A (en) * | 1992-04-03 | 1993-05-04 | Bristol-Meyers Squibb Company | 7-oxypropylsulfonamido-imidazo[4,5-b]quinolin-2-ones |
| US5158958A (en) * | 1992-04-03 | 1992-10-27 | Bristol-Myers Squibb Company | Imidazo[4,5-b]quinolinyl oxy alkyl sulfonyl piperidine derivatives |
| US5552267A (en) * | 1992-04-03 | 1996-09-03 | The Trustees Of Columbia University In The City Of New York | Solution for prolonged organ preservation |
| US5348960A (en) * | 1992-04-03 | 1994-09-20 | Bristol-Myers Squibb Company | Imidazo[4,5-b]quinolinyl oxy alkyl tetrazolyl piperidine derivatives |
| TW593317B (en) * | 1993-06-21 | 2004-06-21 | Janssen Pharmaceutica Nv | Positive cardiac inotropic and lusitropic pyrroloquinolinone derivatives |
| CN1048015C (zh) * | 1993-07-06 | 2000-01-05 | 美国辉瑞有限公司 | 双环四氢吡唑并吡啶类化合物 |
| TW530047B (en) * | 1994-06-08 | 2003-05-01 | Pfizer | Corticotropin releasing factor antagonists |
| US6664264B2 (en) * | 2000-12-08 | 2003-12-16 | 3M Innovative Properties Company | Thioether substituted imidazoquinolines |
| AU2004266641A1 (en) | 2003-08-12 | 2005-03-03 | 3M Innovative Properties Company | Oxime substituted imidazo-containing compounds |
| ES2406730T3 (es) | 2003-08-27 | 2013-06-07 | 3M Innovative Properties Company | Imidazoquinolinas sustituidas con ariloxi y arilalquilenoxi |
| WO2005023190A2 (en) | 2003-09-05 | 2005-03-17 | 3M Innovative Properties Company | Treatment for cd5+ b cell lymphoma |
| US7544697B2 (en) | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
| SG149828A1 (en) * | 2003-10-03 | 2009-02-27 | 3M Innovative Properties Co | Alkoxy substituted imidazoquinolines |
| JP2007511535A (ja) * | 2003-11-14 | 2007-05-10 | スリーエム イノベイティブ プロパティズ カンパニー | ヒドロキシルアミン置換イミダゾ環化合物 |
| CA2545774A1 (en) | 2003-11-14 | 2005-06-02 | 3M Innovative Properties Company | Oxime substituted imidazo ring compounds |
| KR101130928B1 (ko) | 2003-11-25 | 2012-04-12 | 쓰리엠 이노베이티브 프로퍼티즈 컴파니 | 치환된 이미다조 고리 시스템 및 방법 |
| JP2007517035A (ja) | 2003-12-29 | 2007-06-28 | スリーエム イノベイティブ プロパティズ カンパニー | アリールアルケニルおよびアリールアルキニル置換されたイミダゾキノリン |
| CA2551399A1 (en) | 2003-12-30 | 2005-07-21 | 3M Innovative Properties Company | Imidazoquinolinyl, imidazopyridinyl, and imidazonaphthyridinyl sulfonamides |
| TW200612932A (en) | 2004-03-24 | 2006-05-01 | 3M Innovative Properties Co | Amide substituted imidazopyridines, imidazoquinolines, and imidazonaphthyridines |
| US8017779B2 (en) | 2004-06-15 | 2011-09-13 | 3M Innovative Properties Company | Nitrogen containing heterocyclyl substituted imidazoquinolines and imidazonaphthyridines |
| US7897609B2 (en) | 2004-06-18 | 2011-03-01 | 3M Innovative Properties Company | Aryl substituted imidazonaphthyridines |
| US8026366B2 (en) | 2004-06-18 | 2011-09-27 | 3M Innovative Properties Company | Aryloxy and arylalkyleneoxy substituted thiazoloquinolines and thiazolonaphthyridines |
| US7915281B2 (en) | 2004-06-18 | 2011-03-29 | 3M Innovative Properties Company | Isoxazole, dihydroisoxazole, and oxadiazole substituted imidazo ring compounds and method |
| JP4769810B2 (ja) * | 2004-09-14 | 2011-09-07 | ノバルティス ヴァクシンズ アンド ダイアグノスティクス， インコーポレイテッド | イミダゾキノリン化合物 |
| WO2006074003A2 (en) | 2004-12-30 | 2006-07-13 | 3M Innovative Properties Company | CHIRAL FUSED [1,2]IMIDAZO[4,5-c] RING COMPOUNDS |
| CA2594674C (en) | 2004-12-30 | 2016-05-17 | 3M Innovative Properties Company | Substituted chiral fused [1,2]imidazo[4,5-c] ring compounds |
| JP2008530022A (ja) | 2005-02-04 | 2008-08-07 | コーリー ファーマシューティカル グループ，インコーポレイテッド | 免疫反応調節物質を含む水性ゲル処方物 |
| US7968563B2 (en) | 2005-02-11 | 2011-06-28 | 3M Innovative Properties Company | Oxime and hydroxylamine substituted imidazo[4,5-c] ring compounds and methods |
| US7943610B2 (en) | 2005-04-01 | 2011-05-17 | 3M Innovative Properties Company | Pyrazolopyridine-1,4-diamines and analogs thereof |
| JP2008538550A (ja) | 2005-04-01 | 2008-10-30 | コーリー ファーマシューティカル グループ，インコーポレイテッド | ウイルス感染および腫瘍性疾患を処置するためのサイトカイン生合成の調節因子としての１−置換ピラゾロ（３，４−ｃ）環状化合物 |
| WO2008008432A2 (en) | 2006-07-12 | 2008-01-17 | Coley Pharmaceutical Group, Inc. | Substituted chiral fused( 1,2) imidazo (4,5-c) ring compounds and methods |
| US8227603B2 (en) | 2006-08-01 | 2012-07-24 | Cytokinetics, Inc. | Modulating skeletal muscle |
| US8299248B2 (en) | 2006-08-02 | 2012-10-30 | Cytokinetics, Incorporated | Certain 1H-imidazo[4,5-b]pyrazin-2(3H)-ones and 1H-imidazo[4,5-b]pyrazin-2-ols and methods for their use |
| DK2583970T3 (en) | 2006-08-02 | 2015-11-16 | Cytokinetics Inc | Certain chemical entities, compositions, and methods comprising imidazopyrimidines |
| WO2008121333A1 (en) * | 2007-03-30 | 2008-10-09 | Cytokinetics, Incorporated | Certain chemical entities, compositions and methods |
| SG10201605707UA (en) | 2011-07-13 | 2016-09-29 | Cytokinetics Inc | Combination als therapy |
| WO2024149378A1 (zh) * | 2023-01-13 | 2024-07-18 | 上海超阳药业有限公司 | 喹啉酮化合物和萘啶酮化合物及其用途 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3932407A (en) * | 1973-11-19 | 1976-01-13 | Bristol-Myers Company | Optionally substituted 1,2,3,5-tetrahydroimidezo(2,1-b)-quinazolin-2-ones and 6(H)-1,2,3,4-tetrahydropyimido(2,1-b)quinazolin-2-ones |
-
1986
- 1986-02-26 US US06/832,212 patent/US4668686A/en not_active Expired - Fee Related
- 1986-03-26 CA CA000505136A patent/CA1298836C/en not_active Expired - Fee Related
- 1986-04-18 NZ NZ215885A patent/NZ215885A/xx unknown
- 1986-04-21 AU AU56413/86A patent/AU592983B2/en not_active Ceased
- 1986-04-22 FI FI861684A patent/FI83316C/fi not_active IP Right Cessation
- 1986-04-22 IL IL78581A patent/IL78581A0/xx not_active IP Right Cessation
- 1986-04-23 EG EG237/86A patent/EG18104A/xx active
- 1986-04-23 CN CN86102747A patent/CN1016175B/zh not_active Expired
- 1986-04-24 GR GR861086A patent/GR861086B/el unknown
- 1986-04-24 LU LU86406A patent/LU86406A1/fr unknown
- 1986-04-24 DK DK190986A patent/DK164868C/da not_active IP Right Cessation
- 1986-04-24 SE SE8601907A patent/SE461468B/sv not_active IP Right Cessation
- 1986-04-24 BE BE0/216585A patent/BE904671A/fr not_active IP Right Cessation
- 1986-04-24 IT IT8620206A patent/IT1215651B/it active
- 1986-04-24 FR FR868605966A patent/FR2581065B1/fr not_active Expired - Fee Related
- 1986-04-24 ES ES554336A patent/ES8708229A1/es not_active Expired
- 1986-04-24 SU SU864027355A patent/SU1450746A3/ru active
- 1986-04-24 PT PT82460A patent/PT82460B/pt not_active IP Right Cessation
- 1986-04-24 NL NL8601053A patent/NL8601053A/xx not_active Application Discontinuation
- 1986-04-24 NO NO861617A patent/NO163406C/no unknown
- 1986-04-24 GB GB8610037A patent/GB2174987B/en not_active Expired
- 1986-04-24 CH CH1679/86A patent/CH675722A5/de not_active IP Right Cessation
- 1986-04-25 AT AT0112186A patent/AT390257B/de not_active IP Right Cessation
- 1986-04-25 KR KR1019860003204A patent/KR940000828B1/ko not_active Expired - Lifetime
- 1986-04-25 OA OA58845A patent/OA08242A/xx unknown
- 1986-04-25 HU HU861723A patent/HU195813B/hu not_active IP Right Cessation
- 1986-04-25 DE DE19863614132 patent/DE3614132A1/de not_active Ceased
-
1987
- 1987-02-27 SU SU874202071A patent/SU1470192A3/ru active
- 1987-05-14 ES ES557552A patent/ES8802521A1/es not_active Expired
- 1987-05-14 ES ES557551A patent/ES8801829A1/es not_active Expired
- 1987-06-23 YU YU116787A patent/YU46054B/sh unknown
- 1987-09-25 SU SU874203391A patent/SU1560056A3/ru active
- 1987-09-29 MY MYPI87002266A patent/MY102086A/en unknown
-
1991
- 1991-04-30 DK DK080291A patent/DK165248C/da not_active IP Right Cessation
- 1991-05-01 DK DK081091A patent/DK165249C/da not_active IP Right Cessation
-
1992
- 1992-03-10 SG SG290/92A patent/SG29092G/en unknown
- 1992-08-27 HK HK644/92A patent/HK64492A/xx unknown
- 1992-11-06 CY CY1641A patent/CY1641A/en unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1298836C (en) | Imidazoquinoline antithrombogenic cardiotonic agents | |
| AU603577B2 (en) | Imidazoquinolinylether derivatives | |
| CA1309095C (en) | Aminoimidazoquinoline derivatives | |
| IE59309B1 (en) | New quinazoline derivatives, process for their production and pharmaceutical compositions comprising them | |
| NO179868B (no) | Analogifremgangsmåte for fremstilling av terapeutisk aktive kondenserte heterocykliske forbindelser | |
| MXPA00007058A (es) | Nuevos compuestos de -carbolina, un proceso para su preparacion y composiciones farmaceuticas que los contienen. | |
| US3993656A (en) | 1,8-Naphthyridine compounds | |
| IE55156B1 (en) | Pharmacologically active pyrazolo(4,3-c)pyridines | |
| IE871767L (en) | PYRROLO £1,2-c| THIAZOLE DERIVATIVES | |
| IE61045B1 (en) | 4-aryl-5-carbamoyl-1, 4-dihydropyridines | |
| NO823026L (no) | 2(1h)-pyridinoner og fremgangsmaate for deres fremstilling | |
| CA1275100A (en) | ANTIPSYCHOTIC .gamma.-CARBOLINES | |
| PT90907B (pt) | Processo para a preparacao de novas 4,5,7,8-tetra-hidro-6h-tiazolo {5,4-d} azepinas e de composicoes farmaceuticas que as contem | |
| NZ207981A (en) | Pyrimidones and pharmaceutical compositions | |
| US20040204418A1 (en) | Fused-polycyclic compounds | |
| NO310872B1 (no) | Aryl- og heteroaryl-alkoksynaftalenderivater og farmasöytiske blandinger | |
| US4260612A (en) | Antiallergic nitrogen bridge-head compounds | |
| US4330543A (en) | Imidazoazines and imidazodiazines | |
| NO893611L (no) | Fremstilling av imidazokinolinonderivater. | |
| JPS6284A (ja) | イミダゾキノリン抗血栓性強心薬 | |
| JPH0428697B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| FI90536B (fi) | Menetelmä uusien terapeuttisesti käyttökelpoisten 2-aminotetrahydroisokinoliinijohdannaisten valmistamiseksi | |
| WO1992012979A1 (en) | 2,4-DIOXO-PYRIDO [2,3-d]PYRIMIDINE-3-ACETIC ACIDS AND ESTERS AND SALTS THEREOF | |
| LU83251A1 (fr) | Derives d'imidazo(4,5-b)pyridine,leur preparation et leur utilisation comme agents cardiotoniques |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKLA | Lapsed |