WO1997044343A1 - Phosphorus containing cythesine derivatives - Google Patents
Phosphorus containing cythesine derivatives Download PDFInfo
- Publication number
- WO1997044343A1 WO1997044343A1 PCT/KZ1996/000002 KZ9600002W WO9744343A1 WO 1997044343 A1 WO1997044343 A1 WO 1997044343A1 KZ 9600002 W KZ9600002 W KZ 9600002W WO 9744343 A1 WO9744343 A1 WO 9744343A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- derivatives
- activity
- phosphorus containing
- compounds
- solution
- Prior art date
Links
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 229910052698 phosphorus Inorganic materials 0.000 title claims abstract description 13
- 239000011574 phosphorus Substances 0.000 title claims abstract description 12
- 150000001875 compounds Chemical class 0.000 abstract description 19
- 230000000694 effects Effects 0.000 abstract description 15
- 230000002443 hepatoprotective effect Effects 0.000 abstract description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 12
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 239000000126 substance Substances 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 9
- 229910052799 carbon Inorganic materials 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 5
- 239000002574 poison Substances 0.000 description 5
- 231100000614 poison Toxicity 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000001553 hepatotropic effect Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 235000019271 petrolatum Nutrition 0.000 description 4
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- CZHYKKAKFWLGJO-UHFFFAOYSA-N dimethyl phosphite Chemical compound COP([O-])OC CZHYKKAKFWLGJO-UHFFFAOYSA-N 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 231100000566 intoxication Toxicity 0.000 description 3
- 230000035987 intoxication Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000029058 respiratory gaseous exchange Effects 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 3
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 102000018832 Cytochromes Human genes 0.000 description 2
- 108010052832 Cytochromes Proteins 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- 150000003797 alkaloid derivatives Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000001362 electron spin resonance spectrum Methods 0.000 description 2
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 231100000572 poisoning Toxicity 0.000 description 2
- 230000000607 poisoning effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- OMIHGPLIXGGMJB-UHFFFAOYSA-N 7-oxabicyclo[4.1.0]hepta-1,3,5-triene Chemical compound C1=CC=C2OC2=C1 OMIHGPLIXGGMJB-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 102100033639 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- 108010053652 Butyrylcholinesterase Proteins 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102100032404 Cholinesterase Human genes 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 244000007853 Sarothamnus scoparius Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000010513 Stupor Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 241000246091 Thermopsis Species 0.000 description 1
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- NNPCWHQMEPPTJV-UHFFFAOYSA-N chloro(dimethoxy)phosphane Chemical compound COP(Cl)OC NNPCWHQMEPPTJV-UHFFFAOYSA-N 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- ANJTVLIZGCUXLD-DTWKUNHWSA-N cytisine Chemical compound C1NC[C@H]2CN3C(=O)C=CC=C3[C@@H]1C2 ANJTVLIZGCUXLD-DTWKUNHWSA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- ANJTVLIZGCUXLD-UHFFFAOYSA-N ent-cytisine Natural products C1NCC2CN3C(=O)C=CC=C3C1C2 ANJTVLIZGCUXLD-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 231100001224 moderate toxicity Toxicity 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 230000036967 uncompetitive effect Effects 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Definitions
- the invention is related to new chemical compounds, in particular to Phosphorus containmg cythesme derivatives showing their hepatoprotective and antienzyme activities.
- alkaloid cythesme (1) extracted firstly from the seeds of broom and thermopsis is now widely used m the medical practise in a state of 0 15% water solution (cytiton) as an anaeleptic agent (Mashkovsky, M D , "Medicine remedies", M, 1977, v 1 p 123)
- a typical property of cythesme is its ability to arouse breathing, that is connected with reflectory stimulation of breathing centre by intensified impulses coming from carotid balls. Simultaneous stimulation of sympathetic knotes and adrenal glands leads to the nse of arterial pressure In this connection the cythesine is recommended to be used in case of breathing and heart activity stoppmg at intoxications.
- the cythesme is widespread m nature It has been found m many plants and its extraction from the plant raw material by the ion exchange method is the mam industrial way to obtam cythesme
- the set aim is attamed by the fact that the phosphorus containing cethysme de ⁇ vatives m the general form have been obtained
- 0,0-dialkyl-N-cethysenylphosphate is formed in the flow of dry argon and in the presence of t ⁇ ethylamine
- R-CH 3 compounds 6 A .c have been obtained by means of the cethysme interaction with aldehydes and dimethylphosphite under the conditions of Kabachmc-Fild's reaction
- the average lethal dose of the LD 50 was determined on white randombrede mice (320 head by 18-20g each). The preparation was injected once intravenously m the physiological solution or perorally in 1% starch suspension An observation period was 14 days General state of ammals was examined every day, du ⁇ ng the observation period 3 times animals were weighed, descased animals were dissected and macroscopic description was done The determination of LD50 was carried out by the method of analysis As a result of the conducted experiments, it has been found that LD 50
- This preparation is a complex set of substances and contams a sum of flavonoids, phosphohpides, nicotineamid and various vitamines
- the hepatoprotective activity of the stated preparation at acute toxical hepatitis was studied with 4 groups of white randombredory rat males weighing 120-150 grams by 10 specimens each The first group Animals were subjected to intravenous injection of
- the second group Ammals were subjected to mtravenous injection of 0.1 ml isotomc solution of sodium chloride and then in hour they were subjected to mtra-abdormnal injection of 0.4 ml 40% solution of hepatotropic poison - carbon tetrachloride in petroleum jelly
- the third group Animals were subjected to intravenous injection of 0 1 ml "Essentsialle" solution (50 mg/kg) and then in hour they were subjected to intra-abdominal injection of 0 4 ml 40% CC1 4 solution in petrolleum jelly
- the fourth group Animals were subjected to mtravenous injection of 0 1 ml water solution of the stated substance (50 mg/rg) and then, in hour, they were subjected to intra-abdominal injection of 0 4 ml 40%o CC1 4 m petroleum jelly
- alaninaminotranspherase (ALAT) enxyme and the level of total bilirubin m blood, erythrocyte chemiluminescence filtration, regeneratmg and distrofied cells in sections of liver tissue were investigated
- the erythrocytes extracted from blood were suspended m isotomc sodium chlo ⁇ de solution (by 1 ml 10% erythrocyte suspension in a sample), glow was stimulated with 0 1 ml 5% H 2 0 2 and average a ⁇ thmetic values of an integral area under the curve of chemiluminescence were determmed
- mice To study the preparation effect on mouse survival rate at their intoxication with hepatotropic poison the white randombrede mice were used, males weighing 18-20 grams, three groups by 10 mice each
- Animals of the first group were subjected to intrape ⁇ toneal mjection of 0 1 ml isotomc sodium chloride solution
- Animals of the second group were subjected to mtravenous mjection of 0 1 ml "Essentsialle" solution m a dose 50 mg/kg
- Animals of the third group were subjected to intrape ⁇ toneal injection of 0 1 ml solution of the stated substance in water solution (100 mg/kg)
- the injections were made once An observation period was 5 days
- the survival rate in 5 days was the following
- ACE acethylcholines therase
- BCE butirylcholinestherase
- Activity of P450 cytochrome was determined by two methods: with the rate of hydroxylation of 3.4-benz/a/pyrene, by usmg of fluonmetric determination of forming 4-hydroxybenz/a/pyrene, and with the rate of 7- ethoxyqumarine diethylation by using of fluorimetric determination of 7- hydroxyqumarine formed.
- cethysinylphosphates and cethysinyltiophosphates are ACE inhibitors with mean power and quite effective BCE inhibitors. The most celectivity relatively to BCE was observed for tiophosphate derivatives (pKl - 6.7 and pKl -6.1 correspondingly).
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Glass Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Devices For Indicating Variable Information By Combining Individual Elements (AREA)
Abstract
Description
Claims
Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/194,176 US6194397B1 (en) | 1996-05-20 | 1996-05-20 | Phosphorus containing cytisine derivatives |
AT96925156T ATE182894T1 (en) | 1996-05-20 | 1996-05-20 | PHOSPHOR CONTAINING CYTISINE DERIVATIVES |
EP96925156A EP0857172B1 (en) | 1996-05-20 | 1996-05-20 | Phosphorus containing cythesine derivatives |
DK96925156T DK0857172T3 (en) | 1996-05-20 | 1996-05-20 | Phosphorus-containing cytisine derivatives |
PCT/KZ1996/000002 WO1997044343A1 (en) | 1996-05-20 | 1996-05-20 | Phosphorus containing cythesine derivatives |
PL96331178A PL184934B1 (en) | 1996-05-20 | 1996-05-20 | Phosphoric derivatives of citysin |
ES96925156T ES2138362T4 (en) | 1996-05-20 | 1996-05-20 | DERIVATIVES OF CITISINE WITH CONTENT OF PHOSPHORUS. |
UA99010428A UA59365C2 (en) | 1996-05-20 | 1996-05-20 | phosphorus containing cethysine derivatives |
CA002233632A CA2233632C (en) | 1996-05-20 | 1996-05-20 | Phosphorus containing cythesine derivatives |
DE69603617T DE69603617T2 (en) | 1996-05-20 | 1996-05-20 | CYTISINE DERIVATIVES CONTAINING PHOSPHORUS |
GR990402838T GR3031743T3 (en) | 1996-05-20 | 1999-11-03 | Phosphorus containing cythesine derivatives |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/KZ1996/000002 WO1997044343A1 (en) | 1996-05-20 | 1996-05-20 | Phosphorus containing cythesine derivatives |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1997044343A1 true WO1997044343A1 (en) | 1997-11-27 |
Family
ID=19720829
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KZ1996/000002 WO1997044343A1 (en) | 1996-05-20 | 1996-05-20 | Phosphorus containing cythesine derivatives |
Country Status (11)
Country | Link |
---|---|
US (1) | US6194397B1 (en) |
EP (1) | EP0857172B1 (en) |
AT (1) | ATE182894T1 (en) |
CA (1) | CA2233632C (en) |
DE (1) | DE69603617T2 (en) |
DK (1) | DK0857172T3 (en) |
ES (1) | ES2138362T4 (en) |
GR (1) | GR3031743T3 (en) |
PL (1) | PL184934B1 (en) |
UA (1) | UA59365C2 (en) |
WO (1) | WO1997044343A1 (en) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19960223A1 (en) * | 1999-07-15 | 2001-01-18 | Mann & Hummel Filter | Suction module for an internal combustion engine |
US20060211649A1 (en) * | 2005-03-21 | 2006-09-21 | Eric Marchewitz | Use of cytisine for enhancing physical performance |
US8123051B2 (en) * | 2009-07-20 | 2012-02-28 | Target Brands, Inc. | Display apparatus for securely displaying a product |
PL408608A1 (en) | 2014-06-18 | 2015-12-21 | Pharmacia Polonica Spółka Z Ograniczoną Odpowiedzialnością | Stable permanent pharmaceutical composition of cytisine and method for producing it |
-
1996
- 1996-05-20 DE DE69603617T patent/DE69603617T2/en not_active Expired - Fee Related
- 1996-05-20 ES ES96925156T patent/ES2138362T4/en not_active Expired - Lifetime
- 1996-05-20 UA UA99010428A patent/UA59365C2/en unknown
- 1996-05-20 EP EP96925156A patent/EP0857172B1/en not_active Expired - Lifetime
- 1996-05-20 PL PL96331178A patent/PL184934B1/en unknown
- 1996-05-20 CA CA002233632A patent/CA2233632C/en not_active Expired - Fee Related
- 1996-05-20 AT AT96925156T patent/ATE182894T1/en active
- 1996-05-20 DK DK96925156T patent/DK0857172T3/en active
- 1996-05-20 WO PCT/KZ1996/000002 patent/WO1997044343A1/en active Application Filing
- 1996-05-20 US US09/194,176 patent/US6194397B1/en not_active Expired - Fee Related
-
1999
- 1999-11-03 GR GR990402838T patent/GR3031743T3/en unknown
Non-Patent Citations (5)
Title |
---|
CHEMICAL ABSTRACTS, vol. 075, no. 17, 25 October 1971, Columbus, Ohio, US; abstract no. 110494, SHAIMARDANOV R A ET AL: "New N-substituted derivatives of cytisine" XP002022847 * |
FAZYLOV S D ET AL: "Formation of N-[(dialkoxyphosphoryl)methyl] derivatives of cytisine and their internal salts under conditions of Kabachnik-Fields reaction", ZH. OBSHCH. KHIM. (ZOKHA4,0044460X);96; VOL.66 (2); PP.238-239, NAT. ACAD. SCI. KAZAKHSTAN;INST. ORGANIC SYNTHESIS AND COAL CHEMISTRY; KARAGANDA; KAZAKHSTAN (KZ), XP002022846 * |
GAZALIEV A M ET AL: "Synthesis and antienzymic activity of new phosphorus-containing derivatives of the alkaloid cytisine", IZV. NATS. AKAD. NAUK RESP. KAZ., SER. KHIM. (INRKES);94; (3); PP.80-4, INST. ORG. SINIT. UGLEKHIM.;KARAGANDA; KAZAKHSTAN (KZ), XP002022845 * |
GAZALIEV A M ET AL: "Synthesis and molecular and crystal structure of dimethyl N-cytisinylamidophosphate", ZH. OBSHCH. KHIM. (ZOKHA4,0044460X);92; VOL.62 (2); PP.456-61, INST. ORG. SINT. UGLEKHIM.;KARAGANDA; RUSSIA (RU), XP000611893 * |
KHIM. PRIR. SOEDIN. (KPSUAR);71; VOL.7 (3); PP.383-4, INST. KHIM. RAST. VESCH.;TASHKENT; USSR * |
Also Published As
Publication number | Publication date |
---|---|
CA2233632A1 (en) | 1997-11-27 |
GR3031743T3 (en) | 2000-02-29 |
CA2233632C (en) | 2002-07-16 |
DE69603617T2 (en) | 2000-03-09 |
UA59365C2 (en) | 2003-09-15 |
DE69603617D1 (en) | 1999-09-09 |
ES2138362T4 (en) | 2000-05-16 |
EP0857172B1 (en) | 1999-08-04 |
PL184934B1 (en) | 2003-01-31 |
PL331178A1 (en) | 1999-06-21 |
US6194397B1 (en) | 2001-02-27 |
ES2138362T3 (en) | 2000-01-01 |
EP0857172A1 (en) | 1998-08-12 |
DK0857172T3 (en) | 2000-03-06 |
ATE182894T1 (en) | 1999-08-15 |
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