PH26971A - 6-substituted purinyl piperazine derivatives useful as anti-arrhythmic agents - Google Patents
6-substituted purinyl piperazine derivatives useful as anti-arrhythmic agents Download PDFInfo
- Publication number
- PH26971A PH26971A PH38279A PH38279A PH26971A PH 26971 A PH26971 A PH 26971A PH 38279 A PH38279 A PH 38279A PH 38279 A PH38279 A PH 38279A PH 26971 A PH26971 A PH 26971A
- Authority
- PH
- Philippines
- Prior art keywords
- lower alkyl
- compound
- ary
- phenyl
- halo
- Prior art date
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- -1 6-substituted purinyl piperazine Chemical class 0.000 title claims abstract description 18
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title abstract description 7
- 239000003416 antiarrhythmic agent Substances 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 64
- 238000000034 method Methods 0.000 claims abstract description 33
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 229910052757 nitrogen Inorganic materials 0.000 claims description 35
- 239000000203 mixture Substances 0.000 claims description 33
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 6
- 125000002346 iodo group Chemical group I* 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 230000000747 cardiac effect Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 206010003119 arrhythmia Diseases 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 6
- 229910052736 halogen Inorganic materials 0.000 claims 3
- 150000002367 halogens Chemical class 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 208000019622 heart disease Diseases 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 239000000496 cardiotonic agent Substances 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 111
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 52
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 50
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
- 239000007787 solid Substances 0.000 description 28
- 239000000243 solution Substances 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 24
- 239000000741 silica gel Substances 0.000 description 24
- 229910002027 silica gel Inorganic materials 0.000 description 24
- 239000000047 product Substances 0.000 description 20
- 239000012043 crude product Substances 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000003818 flash chromatography Methods 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical class S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical class C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
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- 239000000725 suspension Substances 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 229960001428 mercaptopurine Drugs 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
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- 239000002585 base Substances 0.000 description 7
- 239000006260 foam Substances 0.000 description 7
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- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 229960005141 piperazine Drugs 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- TTXIFFYPVGWLSE-UHFFFAOYSA-N 1-[bis(4-fluorophenyl)methyl]piperazine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)N1CCNCC1 TTXIFFYPVGWLSE-UHFFFAOYSA-N 0.000 description 4
- 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 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 230000003177 cardiotonic effect Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- WFFQYWAAEWLHJC-UHFFFAOYSA-N mercaptopurine hydrate Chemical compound O.S=C1NC=NC2=C1NC=N2 WFFQYWAAEWLHJC-UHFFFAOYSA-N 0.000 description 4
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- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
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- QSTASPNCKDPSAH-UHFFFAOYSA-N 6-chloro-9-(oxan-2-yl)purine Chemical compound C1=NC=2C(Cl)=NC=NC=2N1C1CCCCO1 QSTASPNCKDPSAH-UHFFFAOYSA-N 0.000 description 3
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
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- AUGBBUFJMAJBGB-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]-3-chloropropan-2-ol Chemical compound C1CN(CC(CCl)O)CCN1CC1=CC=C(OCO2)C2=C1 AUGBBUFJMAJBGB-UHFFFAOYSA-N 0.000 description 2
- PTLFMGDNZYQISN-UHFFFAOYSA-N 1-[bis(4-chlorophenyl)methyl]piperazine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(Cl)=CC=1)N1CCNCC1 PTLFMGDNZYQISN-UHFFFAOYSA-N 0.000 description 2
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- ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical compound ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 2
- 229950006316 6-mercaptopurine monohydrate Drugs 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
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- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 101100007538 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cpc-1 gene Proteins 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- NOQXXYIGRPAZJC-SECBINFHSA-N [(2r)-oxiran-2-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@@H]1OC1 NOQXXYIGRPAZJC-SECBINFHSA-N 0.000 description 1
- NOQXXYIGRPAZJC-VIFPVBQESA-N [(2s)-oxiran-2-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@H]1OC1 NOQXXYIGRPAZJC-VIFPVBQESA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000005792 cardiovascular activity Effects 0.000 description 1
- NEHMKBQYUWJMIP-OUBTZVSYSA-N chloromethane Chemical class Cl[13CH3] NEHMKBQYUWJMIP-OUBTZVSYSA-N 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- NWVNXDKZIQLBNM-UHFFFAOYSA-N diphenylmethylpiperazine Chemical compound C1CNCCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 NWVNXDKZIQLBNM-UHFFFAOYSA-N 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- GKWQBAIVNZBQNJ-UHFFFAOYSA-N ethyl 4-(3-chloro-2-hydroxypropoxy)piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCN(OCC(O)CCl)CC1 GKWQBAIVNZBQNJ-UHFFFAOYSA-N 0.000 description 1
- HQKSINSCHCDMLS-UHFFFAOYSA-N ethyl naphthalene-2-carboxylate Chemical compound C1=CC=CC2=CC(C(=O)OCC)=CC=C21 HQKSINSCHCDMLS-UHFFFAOYSA-N 0.000 description 1
- LNOQURRKNJKKBU-UHFFFAOYSA-N ethyl piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCNCC1 LNOQURRKNJKKBU-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 230000001057 ionotropic effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- JDOZOOBCADNBIJ-UHFFFAOYSA-N lithium;2h-pyridin-2-ide Chemical compound [Li+].C1=CC=N[C-]=C1 JDOZOOBCADNBIJ-UHFFFAOYSA-N 0.000 description 1
- SNHOZPMHMQQMNI-UHFFFAOYSA-N lithium;2h-thiophen-2-ide Chemical compound [Li+].C=1C=[C-]SC=1 SNHOZPMHMQQMNI-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- CNHABSNTBAWVIX-UHFFFAOYSA-N naphthalen-2-yl(pyridin-2-yl)methanone Chemical compound C=1C=C2C=CC=CC2=CC=1C(=O)C1=CC=CC=N1 CNHABSNTBAWVIX-UHFFFAOYSA-N 0.000 description 1
- BIVRXKDHCPNHTK-UHFFFAOYSA-N naphthalen-2-yl-pyridin-2-yl-thiophen-2-ylmethanol Chemical compound C=1C=C2C=CC=CC2=CC=1C(C=1N=CC=CC=1)(O)C1=CC=CS1 BIVRXKDHCPNHTK-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- NOQXXYIGRPAZJC-UHFFFAOYSA-N oxiran-2-ylmethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1OC1 NOQXXYIGRPAZJC-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- AJYOOHCNOXWTKJ-UHFFFAOYSA-N p-Chlorobenzhydrol Chemical compound C=1C=C(Cl)C=CC=1C(O)C1=CC=CC=C1 AJYOOHCNOXWTKJ-UHFFFAOYSA-N 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 229960003641 piperazine hydrate Drugs 0.000 description 1
- 230000009090 positive inotropic effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011110 re-filtration Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 210000005241 right ventricle Anatomy 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
-
- 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
-
- 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
-
- 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
- A61P9/06—Antiarrhythmics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/28—Oxygen atom
- C07D473/30—Oxygen atom attached in position 6, e.g. hypoxanthine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/36—Sulfur atom
- C07D473/38—Sulfur atom attached in position 6
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/163,487 US4876257A (en) | 1988-03-03 | 1988-03-03 | 6-Substituted purinyl piperazine derivatives useful as cardiotonic and antiarrhythmic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PH26971A true PH26971A (en) | 1992-12-28 |
Family
ID=22590215
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PH38279A PH26971A (en) | 1988-03-03 | 1989-03-03 | 6-substituted purinyl piperazine derivatives useful as anti-arrhythmic agents |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US4876257A (ko) |
| EP (1) | EP0331511B1 (ko) |
| JP (1) | JPH0826019B2 (ko) |
| KR (1) | KR940002822B1 (ko) |
| CN (1) | CN1031056C (ko) |
| AT (1) | ATE92067T1 (ko) |
| AU (1) | AU614583B2 (ko) |
| DE (1) | DE68907750T2 (ko) |
| DK (1) | DK101589A (ko) |
| ES (1) | ES2059724T3 (ko) |
| FI (1) | FI92587C (ko) |
| HU (1) | HU205760B (ko) |
| IE (1) | IE63457B1 (ko) |
| IL (1) | IL89458A (ko) |
| MY (1) | MY104959A (ko) |
| NO (1) | NO171500C (ko) |
| NZ (1) | NZ228167A (ko) |
| PH (1) | PH26971A (ko) |
| PT (1) | PT89903B (ko) |
| ZA (1) | ZA891623B (ko) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5057517A (en) * | 1987-07-20 | 1991-10-15 | Merck & Co., Inc. | Piperazinyl derivatives of purines and isosteres thereof as hypoglycemic agents |
| US4885300A (en) * | 1988-03-03 | 1989-12-05 | Ortho Pharmaceutical Corporation | 4-Substituted pyrazolo[3,4-D]pyrimidine derivatives |
| US5164390A (en) * | 1988-03-03 | 1992-11-17 | Ortho Pharmaceutical Corporation | 6-substituted purinyl piperazine derivatives |
| US5021574A (en) * | 1988-03-03 | 1991-06-04 | Ortho Pharmaceutical Corporation | 6-substituted purinyl piperazine derivatives |
| AU648070B2 (en) * | 1990-04-23 | 1994-04-14 | Ortho Pharmaceutical Corporation | Process for preparing optically active isomers of 6-substituted purinyl piperazine derivatives |
| US5215987A (en) * | 1990-04-23 | 1993-06-01 | Ortho Pharmaceutical Corporation | Substituted benzhydryl 2-hydroxypropyl piperazine derivatives |
| NZ237766A (en) | 1990-04-23 | 1993-03-26 | Ortho Pharma Corp | Process for preparing optically active isomers of 6-substituted purinyl-piperazine or -piperidine derivatives; optically active intermediates |
| NZ238122A (en) * | 1990-05-23 | 1994-01-26 | Ortho Pharma Corp | 6-substituted purinyl piperazine derivatives and pharmaceutical |
| US5252569A (en) * | 1990-05-23 | 1993-10-12 | Ortho Pharmaceutical Corporation | 6-substituted purinyl piperazine derivatives |
| CA2129995C (en) * | 1992-02-13 | 2000-04-11 | Albert A. Carr | Piperidinyl thiacyclic derivatives |
| WO1993023386A1 (en) * | 1992-05-15 | 1993-11-25 | Mitsui Toatsu Chemicals, Incorporated | Process for producing glycide derivative |
| ZA9610736B (en) * | 1995-12-22 | 1997-06-27 | Warner Lambert Co | 2-Substituted piperidine analogs and their use as subtypeselective nmda receptor antagonists |
| AU4219897A (en) * | 1996-09-18 | 1998-04-14 | Daiso Co. Ltd. | Process for the preparation of 3-amino-2-hydroxy-1-propyl ethers |
| ATE229011T1 (de) * | 1996-09-18 | 2002-12-15 | Daiso Co Ltd | Verfahren zur herstellung von glycidylethern |
| WO1999002162A1 (en) * | 1997-07-12 | 1999-01-21 | Cancer Research Campaign Technology Limited | Cyclin dependent kinase inhibiting purine derivatives |
| KR20030025153A (ko) * | 2001-09-19 | 2003-03-28 | 이보섭 | 지방족 또는 방향족 관능기를 갖는 6-치환 아미노퓨린유도체 및 이를 함유한 화장료 조성물 |
| JP2006515891A (ja) * | 2003-01-17 | 2006-06-08 | シーブイ・セラピューティクス・インコーポレイテッド | 循環器疾患の処置に有効な置換ヘテロ環化合物 |
| PL3641769T3 (pl) | 2017-06-20 | 2022-09-26 | Imbria Pharmaceuticals, Inc. | Pochodna 1-[(2,3,4-trimetoksyfenylo)metylo]piperazyny, jej kompozycje oraz sposoby zwiększania wydajności metabolizmu serca |
| US11780811B2 (en) | 2020-06-30 | 2023-10-10 | Imbria Pharmaceuticals, Inc. | Methods of synthesizing 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethyl pyridine-3-carboxylate |
| US11530184B2 (en) | 2020-06-30 | 2022-12-20 | Imbria Pharmaceuticals, Inc. | Crystal forms of 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethyl pyridine-3-carboxylate |
| US11883396B2 (en) | 2021-05-03 | 2024-01-30 | Imbria Pharmaceuticals, Inc. | Methods of treating kidney conditions using modified forms of trimetazidine |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3238207A (en) * | 1960-03-01 | 1966-03-01 | Burroughs Wellcome Co | 6-oxyorganopurines and method of preparing them |
| US3232937A (en) * | 1962-08-02 | 1966-02-01 | Burroughs Wellcome Co | 6-benzylmercaptopurines |
| US3135754A (en) * | 1962-08-09 | 1964-06-02 | Burroughs Wellcome Co | Purine derivatives |
| GB1133989A (en) * | 1964-12-08 | 1968-11-20 | Chugai Pharmaceutical Co Ltd | Theophylline derivatives, their salts and process for preparing the same |
| DE1620576A1 (de) * | 1966-11-25 | 1970-02-26 | Troponwerke Dinklage & Co | Verfahren zur Herstellung von Theophyllin- und Theobrominverbindungen |
| GB1289287A (ko) * | 1969-03-28 | 1972-09-13 | ||
| DE2334009A1 (de) * | 1973-07-04 | 1975-01-23 | Boehringer Mannheim Gmbh | Purin-derivate sowie verfahren zu ihrer herstellung |
| US4189579A (en) * | 1977-05-20 | 1980-02-19 | The Dow Chemical Company | Aminoalkylthiopurines |
| US4426383A (en) * | 1980-09-04 | 1984-01-17 | Eisai Co., Ltd. | Theophylline and theobromine derivatives |
| DE3200304A1 (de) * | 1981-01-16 | 1982-08-26 | Sandoz-Patent-GmbH, 7850 Lörrach | 3-aminopropoxyaryl-derivate, ihre herstellung und sie enthaltende arzneimittel |
| IT1161591B (it) * | 1982-03-02 | 1987-03-18 | Eisai Co Ltd | Agenti antiflogistici/antipiretici/analgesici contenenti derivati di teobromina o teofillina come ingrediente attivo |
| DK157135C (da) * | 1982-04-07 | 1990-04-02 | Pfizer | Analogifremgangsmaade til fremstilling af 1,2,4-triazol-forbindelser eller farmaceutisk acceptable syreadditionssalte deraf |
| DE3703633A1 (de) * | 1986-02-14 | 1987-08-20 | Sandoz Ag | Purin-derivate, ihre herstellung und sie enthaltende arzneimittel |
| US4710572A (en) * | 1986-07-30 | 1987-12-01 | American Home Products Corporation | Histamine H1 antagonists |
-
1988
- 1988-03-03 US US07/163,487 patent/US4876257A/en not_active Expired - Fee Related
-
1989
- 1989-02-28 NZ NZ228167A patent/NZ228167A/xx unknown
- 1989-03-01 AU AU30882/89A patent/AU614583B2/en not_active Ceased
- 1989-03-02 IE IE68489A patent/IE63457B1/en not_active IP Right Cessation
- 1989-03-02 MY MYPI89000259A patent/MY104959A/en unknown
- 1989-03-02 NO NO890893A patent/NO171500C/no unknown
- 1989-03-02 IL IL89458A patent/IL89458A/xx not_active IP Right Cessation
- 1989-03-02 ZA ZA891623A patent/ZA891623B/xx unknown
- 1989-03-02 FI FI891003A patent/FI92587C/fi not_active IP Right Cessation
- 1989-03-02 DK DK101589A patent/DK101589A/da unknown
- 1989-03-03 AT AT89302141T patent/ATE92067T1/de not_active IP Right Cessation
- 1989-03-03 CN CN89102516A patent/CN1031056C/zh not_active Expired - Fee Related
- 1989-03-03 PH PH38279A patent/PH26971A/en unknown
- 1989-03-03 JP JP1051804A patent/JPH0826019B2/ja not_active Expired - Lifetime
- 1989-03-03 HU HU891033A patent/HU205760B/hu not_active IP Right Cessation
- 1989-03-03 EP EP89302141A patent/EP0331511B1/en not_active Expired - Lifetime
- 1989-03-03 KR KR1019890002603A patent/KR940002822B1/ko not_active IP Right Cessation
- 1989-03-03 ES ES89302141T patent/ES2059724T3/es not_active Expired - Lifetime
- 1989-03-03 PT PT89903A patent/PT89903B/pt not_active IP Right Cessation
- 1989-03-03 DE DE89302141T patent/DE68907750T2/de not_active Expired - Fee Related
Also Published As
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