DK171788B1 - 1-Acyl-3-[4-(2-pyrimidinyl)-1-piperazinyl]propan-forbindelser, og deres anvendelse til fremstilling af angstdæmpende lægemidler og farmaceutiske præparater indeholdende disse forbindelser - Google Patents

1-Acyl-3-[4-(2-pyrimidinyl)-1-piperazinyl]propan-forbindelser, og deres anvendelse til fremstilling af angstdæmpende lægemidler og farmaceutiske præparater indeholdende disse forbindelser Download PDF

Info

Publication number: DK171788B1
Authority: DK; Denmark
Prior art keywords: compounds; pyrimidinyl; piperazinyl; preparation; acyl
Prior art date: 1987-10-26

Application number

DK591488A

Other languages

Danish (da)

English (en)

Other versions

DK591488A (da

DK591488D0 (da

Inventor

Jr Willard Mckowan Welch

Original Assignee

Pfizer

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1987-10-26

Filing date

1988-10-25

Publication date

1997-05-26

1988-10-25 Application filed by Pfizer filed Critical Pfizer

1988-10-25 Publication of DK591488D0 publication Critical patent/DK591488D0/da

1989-04-27 Publication of DK591488A publication Critical patent/DK591488A/da

1997-05-26 Application granted granted Critical

1997-05-26 Publication of DK171788B1 publication Critical patent/DK171788B1/da

Links

150000001875 compounds Chemical class 0.000 title claims description 33
239000002249 anxiolytic agent Substances 0.000 title claims description 7
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
238000002360 preparation method Methods 0.000 title description 9
229940125713 antianxiety drug Drugs 0.000 title 1
239000002253 acid Substances 0.000 claims abstract description 16
150000003839 salts Chemical class 0.000 claims abstract description 14
208000019901 Anxiety disease Diseases 0.000 claims description 7
230000036506 anxiety Effects 0.000 claims description 5
230000000949 anxiolytic effect Effects 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 2
125000000623 heterocyclic group Chemical group 0.000 abstract 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
241001465754 Metazoa Species 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
238000012360 testing method Methods 0.000 description 6
239000000203 mixture Substances 0.000 description 5
238000010992 reflux Methods 0.000 description 5
230000035939 shock Effects 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
150000001412 amines Chemical class 0.000 description 4
238000005859 coupling reaction Methods 0.000 description 4
230000035622 drinking Effects 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
238000000034 method Methods 0.000 description 4
239000000047 product Substances 0.000 description 4
239000000376 reactant Substances 0.000 description 4
239000007787 solid Substances 0.000 description 4
FZMKTOMLRMRZFO-UHFFFAOYSA-N 4-(4-pyrimidin-2-ylpiperazin-1-ium-1-yl)butanoate Chemical compound C1CN(CCCC(=O)O)CCN1C1=NC=CC=N1 FZMKTOMLRMRZFO-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
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 3
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
239000012298 atmosphere Substances 0.000 description 3
229940079593 drug Drugs 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 2
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
235000009508 confectionery Nutrition 0.000 description 2
239000007822 coupling agent Substances 0.000 description 2
239000000945 filler Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
125000006517 heterocyclyl carbonyl group Chemical group 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
-1 methoxyethyl Chemical group 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
239000002904 solvent Substances 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
MRBFGEHILMYPTF-UHFFFAOYSA-N 1-(2-Pyrimidyl)piperazine Chemical compound C1CNCCN1C1=NC=CC=N1 MRBFGEHILMYPTF-UHFFFAOYSA-N 0.000 description 1
KGRVJHAUYBGFFP-UHFFFAOYSA-N 2,2'-Methylenebis(4-methyl-6-tert-butylphenol) Chemical compound CC(C)(C)C1=CC(C)=CC(CC=2C(=C(C=C(C)C=2)C(C)(C)C)O)=C1O KGRVJHAUYBGFFP-UHFFFAOYSA-N 0.000 description 1
NWJLHLTVRVTJGR-UHFFFAOYSA-N 2-piperazin-4-ium-1-ylpyrimidine;chloride Chemical compound Cl.C1CNCCN1C1=NC=CC=N1 NWJLHLTVRVTJGR-UHFFFAOYSA-N 0.000 description 1
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
NUWZXWQYCYJNQV-UHFFFAOYSA-N 4-(4-pyrimidin-2-ylpiperazin-1-yl)butanoic acid;dihydrochloride Chemical compound Cl.Cl.C1CN(CCCC(=O)O)CCN1C1=NC=CC=N1 NUWZXWQYCYJNQV-UHFFFAOYSA-N 0.000 description 1
XPMNMZWZQBMWHP-UHFFFAOYSA-N 4-(4-pyrimidin-2-ylpiperazin-1-yl)butanoic acid;hydrochloride Chemical compound Cl.C1CN(CCCC(=O)O)CCN1C1=NC=CC=N1 XPMNMZWZQBMWHP-UHFFFAOYSA-N 0.000 description 1
ABFDTYJJUSUWRB-UHFFFAOYSA-N 4-[[4-(dimethylamino)phenyl]iminomethylideneamino]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1N=C=NC1=CC=C(N(C)C)C=C1 ABFDTYJJUSUWRB-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
102000016726 Coat Protein Complex I Human genes 0.000 description 1
108010092897 Coat Protein Complex I Proteins 0.000 description 1
102100035861 Cytosolic 5'-nucleotidase 1A Human genes 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
101000802744 Homo sapiens Cytosolic 5'-nucleotidase 1A Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
150000000994 L-ascorbates Chemical class 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
DTAFLBZLAZYRDX-UHFFFAOYSA-N OOOOOO Chemical compound OOOOOO DTAFLBZLAZYRDX-UHFFFAOYSA-N 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
235000010443 alginic acid Nutrition 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
125000002947 alkylene group Chemical group 0.000 description 1
230000001253 anti-conflict Effects 0.000 description 1
229940005530 anxiolytics Drugs 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
239000002775 capsule Substances 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
UCQFCFPECQILOL-UHFFFAOYSA-N diethyl hydrogen phosphate Chemical compound CCOP(O)(=O)OCC UCQFCFPECQILOL-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
CDTQKBHFXRJDLC-UHFFFAOYSA-N ethyl 4-(4-pyrimidin-2-ylpiperazin-1-yl)butanoate Chemical compound C1CN(CCCC(=O)OCC)CCN1C1=NC=CC=N1 CDTQKBHFXRJDLC-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
229910003480 inorganic solid Inorganic materials 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
150000003893 lactate salts Chemical class 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000010410 layer Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000012264 purified product Substances 0.000 description 1
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000011084 recovery Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/08—Bridged systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Neurology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Anesthesiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Hydrogenated Pyridines (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Graft Or Block Polymers (AREA)
Silicates, Zeolites, And Molecular Sieves (AREA)

DK591488A 1987-10-26 1988-10-25 1-Acyl-3-[4-(2-pyrimidinyl)-1-piperazinyl]propan-forbindelser, og deres anvendelse til fremstilling af angstdæmpende lægemidler og farmaceutiske præparater indeholdende disse forbindelser DK171788B1 (da)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US8702855		1987-10-26
PCT/US1987/002855 WO1989003831A1 (en)	1987-10-26	1987-10-26	Anti-anxiety agents

Publications (3)

Publication Number	Publication Date
DK591488D0 DK591488D0 (da)	1988-10-25
DK591488A DK591488A (da)	1989-04-27
DK171788B1 true DK171788B1 (da)	1997-05-26

Family

ID=22202642

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK591488A DK171788B1 (da)	1987-10-26	1988-10-25	1-Acyl-3-[4-(2-pyrimidinyl)-1-piperazinyl]propan-forbindelser, og deres anvendelse til fremstilling af angstdæmpende lægemidler og farmaceutiske præparater indeholdende disse forbindelser

Country Status (28)

Country	Link
US (1)	US4994455A (cs)
EP (1)	EP0314363B1 (cs)
JP (1)	JPH0643406B2 (cs)
KR (1)	KR900006722B1 (cs)
CN (1)	CN1022246C (cs)
AT (1)	ATE87919T1 (cs)
AU (1)	AU598161B2 (cs)
CA (1)	CA1314881C (cs)
CS (2)	CS274441B2 (cs)
DD (2)	DD283388A5 (cs)
DE (1)	DE3880077T2 (cs)
DK (1)	DK171788B1 (cs)
ES (1)	ES2054823T3 (cs)
FI (1)	FI94638C (cs)
HU (2)	HU206109B (cs)
IE (1)	IE63285B1 (cs)
IL (1)	IL88085A (cs)
MX (1)	MX173180B (cs)
MY (1)	MY103435A (cs)
NO (2)	NO901652L (cs)
NZ (1)	NZ226691A (cs)
PH (1)	PH25106A (cs)
PL (2)	PL152117B1 (cs)
PT (1)	PT88835B (cs)
RU (1)	RU2029768C1 (cs)
WO (1)	WO1989003831A1 (cs)
YU (1)	YU46592B (cs)
ZA (1)	ZA887925B (cs)

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AR242678A1 (es) *	1986-03-05	1993-04-30	Gonzalez Jorge Alberto	Mejoras en instrumentos musicales de cuerda de arco.
US4797488A (en) *	1987-04-03	1989-01-10	American Home Products Corporation	Psychotropic polycyclic imides
SE8803429D0 (sv) *	1988-09-28	1988-09-28	Pharmacia Ab	Novel pyridyl- and pyrimidyl derivatives
EP0376633B1 (en) *	1988-12-28	1994-10-12	Suntory Limited	Benzoxazepine derivatives
US5114936A (en) *	1990-08-23	1992-05-19	Hoechst-Roussel Pharmaceuticals Incorporated	6,7-dihydro-3-phenyl-1,2-benzisoxazol-4(5h)-ones and -ols, compositions and pharmaceutical use
ES2099031B1 (es) *	1995-05-31	1997-12-01	Esteve Labor Dr	Nuevos polimorfos de diclorhidrato de lesopitron y sus formas hidratadas, procedimientos de preparacion y composiciones que los contienen.
SK285371B6 (sk) *	1997-12-22	2006-12-07	Bayer Corporation	Aryl- a heteroaryl-substituované heterocyklické močoviny, ich použitie a farmaceutické kompozície sich obsahom
HUP0104432A3 (en) *	1998-02-19	2003-04-28	Kowa Co	Cyclic amide compounds and medicaments containing the same
GB9902989D0 (en) *	1999-02-11	1999-03-31	Zeneca Ltd	Heterocyclic derivatives
UA77526C2 (en) *	2002-06-07	2006-12-15	Sanofi Aventis	Substituted derivatives of 1-piperazineacylpiperidine, a method for the preparation thereof and their use in therapy
FR2862968B1 (fr) *	2003-12-01	2006-08-04	Sanofi Synthelabo	Derives de 4-[(arylmethyl)aminomethyl]piperidine, leur preparation et leur application en therapeutique
FR2862967B1 (fr) *	2003-12-01	2006-08-04	Sanofi Synthelabo	Derives de (4-phenylpiperazin-1-yl)acylpiperidine, leur preparation et leur application en therapeutique
EP2318388A2 (en) *	2008-07-23	2011-05-11	Schering Corporation	Tricyclic spirocycle derivatives and methods of use thereof
US8617801B2 (en) *	2009-06-03	2013-12-31	Carestream Health, Inc.	Film with blue dye

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US2672460A (en) *	1952-06-24	1954-03-16	American Cyanamid Co	Disubstituted piperazines and methods of preparing the same
BE759371A (fr) *	1969-11-24	1971-05-24	Bristol Myers Co	Azaspirodecanediones heterocycliques et procedes pour leur preparation
US4666911A (en) *	1981-07-14	1987-05-19	Taiho Pharmaceutical Company Limited	Allophanoylpiperazine compound and analgesic composition containing same as active ingredient
DE3321969A1 (de) *	1983-06-18	1984-12-20	Troponwerke GmbH & Co KG, 5000 Köln	2-pyrimidinyl-1-piperazin-derivate, verfahren zu ihrer herstellung und diese enthaltende arzneimittel
US4605655A (en) *	1984-03-06	1986-08-12	Bristol-Myers Company	Antipsychotic 1-fluorophenylbutyl-4-(2-pyrimidinyl)piperazine derivatives
JPS6175A (ja) *	1984-03-06	1986-01-06	ブリストル−マイア−ズ　コムパニ−	神経弛緩剤、１‐フルオロフェニルブチル‐４‐（５‐ハロ‐２‐ピリミジニル）ピペラジン誘導体
US4562255A (en) *	1984-03-30	1985-12-31	American Home Products Corporation	Substituted bi-alicyclic imides
US4668687A (en) *	1984-07-23	1987-05-26	Bristol-Myers Company	Psychogeriatric 1-(2-pyrimidinyl)piperazinyl derivatives of 1-pyrrolidin-2-ones
AR242678A1 (es) *	1986-03-05	1993-04-30	Gonzalez Jorge Alberto	Mejoras en instrumentos musicales de cuerda de arco.
US4797488A (en) *	1987-04-03	1989-01-10	American Home Products Corporation	Psychotropic polycyclic imides

1987
- 1987-10-26 HU HU876036A patent/HU206109B/hu not_active IP Right Cessation
- 1987-10-26 MX MX013562A patent/MX173180B/es unknown
- 1987-10-26 HU HU913849A patent/HU208690B/hu not_active IP Right Cessation
- 1987-10-26 WO PCT/US1987/002855 patent/WO1989003831A1/en not_active Ceased
- 1987-10-26 US US07/477,835 patent/US4994455A/en not_active Expired - Lifetime
1988
- 1988-10-17 DE DE8888309725T patent/DE3880077T2/de not_active Expired - Fee Related
- 1988-10-17 AT AT88309725T patent/ATE87919T1/de not_active IP Right Cessation
- 1988-10-17 EP EP88309725A patent/EP0314363B1/en not_active Expired - Lifetime
- 1988-10-17 ES ES88309725T patent/ES2054823T3/es not_active Expired - Lifetime
- 1988-10-19 IL IL88085A patent/IL88085A/xx not_active IP Right Cessation
- 1988-10-21 MY MYPI88001197A patent/MY103435A/en unknown
- 1988-10-24 DD DD88321032A patent/DD283388A5/de not_active IP Right Cessation
- 1988-10-24 PT PT88835A patent/PT88835B/pt not_active IP Right Cessation
- 1988-10-24 CN CN88107386A patent/CN1022246C/zh not_active Expired - Fee Related
- 1988-10-24 DD DD88337989A patent/DD298397A5/de not_active IP Right Cessation
- 1988-10-24 CA CA000581091A patent/CA1314881C/en not_active Expired - Fee Related
- 1988-10-24 ZA ZA887925A patent/ZA887925B/xx unknown
- 1988-10-24 JP JP63268008A patent/JPH0643406B2/ja not_active Expired - Lifetime
- 1988-10-25 NZ NZ226691A patent/NZ226691A/en unknown
- 1988-10-25 PL PL1988275476A patent/PL152117B1/pl unknown
- 1988-10-25 DK DK591488A patent/DK171788B1/da active
- 1988-10-25 IE IE321888A patent/IE63285B1/en not_active IP Right Cessation
- 1988-10-25 AU AU24327/88A patent/AU598161B2/en not_active Ceased
- 1988-10-25 YU YU198988A patent/YU46592B/sh unknown
- 1988-10-25 KR KR1019880013911A patent/KR900006722B1/ko not_active Expired
- 1988-10-25 PL PL1988279558A patent/PL153184B1/pl unknown
- 1988-10-26 PH PH37726A patent/PH25106A/en unknown
- 1988-10-26 CS CS708088A patent/CS274441B2/cs not_active IP Right Cessation
1989
- 1989-03-02 CS CS135189A patent/CS274446B2/cs not_active IP Right Cessation
1990
- 1990-04-11 NO NO90901652A patent/NO901652L/no unknown
- 1990-04-25 FI FI902070A patent/FI94638C/fi not_active IP Right Cessation
- 1990-04-25 NO NO1990901826A patent/NO901826D0/no unknown
- 1990-04-25 RU SU904743942A patent/RU2029768C1/ru active

Also Published As

Publication number	Publication date
EP0314363B1 (en)	1993-04-07
CN1022246C (zh)	1993-09-29
DK591488A (da)	1989-04-27
IL88085A (en)	1993-02-21
PL152117B1 (en)	1990-11-30
KR890006621A (ko)	1989-06-14
PL275476A1 (en)	1989-09-18
IE883218L (en)	1989-04-26
HU913849D0 (en)	1992-03-30
EP0314363A3 (en)	1990-07-11
NZ226691A (en)	1990-04-26
EP0314363A2 (en)	1989-05-03
AU2432788A (en)	1989-04-27
DD298397A5 (de)	1992-02-20
YU198988A (en)	1990-06-30
PT88835B (pt)	1993-01-29
AU598161B2 (en)	1990-06-14
MY103435A (en)	1993-06-30
HU208690B (en)	1993-12-28
CS708088A2 (en)	1990-08-14
JPH0643406B2 (ja)	1994-06-08
IE63285B1 (en)	1995-04-05
CS274446B2 (en)	1991-04-11
CA1314881C (en)	1993-03-23
MX13562A (es)	1993-04-01
CS135189A2 (en)	1990-08-14
FI902070A0 (fi)	1990-04-25
NO901652D0 (no)	1990-04-11
HU206109B (en)	1992-08-28
CN1042148A (zh)	1990-05-16
PH25106A (en)	1991-02-19
WO1989003831A1 (en)	1989-05-05
ATE87919T1 (de)	1993-04-15
HUT58724A (en)	1992-03-30
ES2054823T3 (es)	1994-08-16
DE3880077T2 (de)	1993-07-22
HUT59393A (en)	1992-05-28
FI94638B (fi)	1995-06-30
DE3880077D1 (de)	1993-05-13
CS274441B2 (en)	1991-04-11
JPH01157979A (ja)	1989-06-21
KR900006722B1 (ko)	1990-09-20
DK591488D0 (da)	1988-10-25
RU2029768C1 (ru)	1995-02-27
MX173180B (es)	1994-02-07
NO901652L (no)	1990-04-11
ZA887925B (en)	1990-06-27
PL153184B1 (en)	1991-03-29
YU46592B (sh)	1993-11-16
FI94638C (fi)	1995-10-10
PL279558A1 (en)	1990-01-08
US4994455A (en)	1991-02-19
DD283388A5 (de)	1990-10-10
NO901826D0 (no)	1990-04-25

Publication	Publication Date	Title
Romero et al.	1994	Discovery, synthesis, and bioactivity of bis (heteroaryl) piperazines. 1. A novel class of non-nucleoside HIV-1 reverse transcriptase inhibitors
US11053239B2 (en)	2021-07-06	Compounds as BLC-2-selective apoptosis-inducing agents
CZ289787A3 (cs)	1998-11-11	Substituovaný benzamidový derivát, způsob jeho výroby a farmaceutický prostředek na jeho bázi
CN103159760A (zh)	2013-06-19	作为cftr调控剂的氮杂吲哚衍生物
PL173643B1 (pl)	1998-04-30	Sposób wytwarzania nowych połączonych cyklicznych poliamin o aktywności przeciwko HIV
KR870001027B1 (ko)	1987-05-25	카르복시이미드 유도체의 제조방법
DK175313B1 (da)	2004-08-16	Farmaceutisk middel indeholdende 1-[mono- eller bis(trifluormethyl)-2-pyridinyl]piperaziner
EA019289B1 (ru)	2014-02-28	Производные аминопиридина, аминопиримидина и амино-1,3,5-триазина
FI94638B (fi)	1995-06-30	Menetelmä terapeuttisesti käyttökelpoisten 1-asyyli-3-/4-(2-pyrimidinyyli)-1-piperatsinyyli/propaanien valmistamiseksi
PL144921B1 (en)	1988-07-30	Method of obtaining novel susbtituted pyrolidinone
JPH06500314A (ja)	1994-01-13	トリサイクリックベンゾジアゼピン誘導体及びその製造方法並びにその物を含む医薬用組成物
JPH05504358A (ja)	1993-07-08	置換尿素化合物及びそれらの製法及び使用
US5641772A (en)	1997-06-24	Condensed diazepinones, processes for preparing them and agents containing these compounds for treating diseases of the central nervous system and for promoting cerebral blood circulation
SK38594A3 (en)	1994-12-07	Thiadiazinones
US7659308B2 (en)	2010-02-09	Concentricolide and its derivatives, process for preparing them, pharmaceutical composition comprising the same and its use
DK166022B (da)	1993-03-01	Bis-(piperazinyl- eller homopiperazinyl)-alkaner og syreadditionssalte deraf, fremgangsmaade til deres fremstilling, farmaceutiske praeparater indeholdende forbindelserne, fremgangsmaade til fremstilling af saadanne praeparater og anvendelse af forbindelserne til fremstilling af et farmaceutisk praeparat med antiallergisk og antiinflammatorisk virkning
EP0495889A1 (en)	1992-07-29	IMINOMETHANODIBENZO(a,d)CYCLOHEPTENE DERIVATIVES AS NEUROPROTECTANT AGENTS
US4812472A (en)	1989-03-14	Isoxazole compounds and pharmaceutical compositions containing them for treatment and prophylaxis of retroviruses diseases
JPS6256874B2 (cs)	1987-11-27
GB2162843A (en)	1986-02-12	Piperazine derivatives
AU604085B2 (en)	1990-12-06	Isoxazole derivatives with antiviral activities and pharmaceutical products containing these
KR102789906B1 (ko)	2025-04-01	신규 피리미딘 유도체
IE44696B1 (en)	1982-02-24	Pyrodoxine derivatives
JP3000295B2 (ja)	2000-01-17	ピロロ〔２，１―ｂ〕チアゾール誘導体及びこれを含有する肝疾患予防・治療剤
JPH04270222A (ja)	1992-09-25	脳機能改善剤