PL179170B1 - Nowe zwiazki,pochodne genisteiny PL PL PL PL - Google Patents
Nowe zwiazki,pochodne genisteiny PL PL PL PLInfo
- Publication number
- PL179170B1 PL179170B1 PL95310486A PL31048695A PL179170B1 PL 179170 B1 PL179170 B1 PL 179170B1 PL 95310486 A PL95310486 A PL 95310486A PL 31048695 A PL31048695 A PL 31048695A PL 179170 B1 PL179170 B1 PL 179170B1
- Authority
- PL
- Poland
- Prior art keywords
- genistein
- general formula
- hydrogen
- derivatives
- alkyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 20
- 150000002272 genistein Chemical class 0.000 title abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 8
- 239000001257 hydrogen Substances 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 229930004065 genistein derivative Natural products 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 150000002273 genistein derivatives Chemical class 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229960003444 immunosuppressant agent Drugs 0.000 abstract description 6
- 239000003018 immunosuppressive agent Substances 0.000 abstract description 6
- 230000001861 immunosuppressant effect Effects 0.000 abstract description 5
- 230000000259 anti-tumor effect Effects 0.000 abstract description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 2
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 150000002431 hydrogen Chemical class 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 description 11
- 210000004698 lymphocyte Anatomy 0.000 description 10
- 229940045109 genistein Drugs 0.000 description 9
- 235000006539 genistein Nutrition 0.000 description 9
- ZCOLJUOHXJRHDI-CMWLGVBASA-N genistein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZCOLJUOHXJRHDI-CMWLGVBASA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 4
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 108010062580 Concanavalin A Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- OTAFHZMPRISVEM-UHFFFAOYSA-N benzo-gamma-pyrone Natural products C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 2
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 2
- 101000835093 Homo sapiens Transferrin receptor protein 1 Proteins 0.000 description 2
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 2
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 241000894007 species Species 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 1
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 102000006354 HLA-DR Antigens Human genes 0.000 description 1
- 108010058597 HLA-DR Antigens Proteins 0.000 description 1
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 1
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 241000009298 Trigla lyra Species 0.000 description 1
- 238000011316 allogeneic transplantation Methods 0.000 description 1
- -1 amine salts Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 150000002780 morpholines Chemical class 0.000 description 1
- 239000003075 phytoestrogen Substances 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 239000003375 plant hormone Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 238000002689 xenotransplantation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/34—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only
- C07D311/36—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only not hydrogenated in the hetero ring, e.g. isoflavones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
Abstract
1. Nowe zwiazki, pochodne genisteiny, o wzorze ogólnym 1, w którym R , R2 , R3 sa takie same lub rózne, R1 oznacza atom wodo- ru lub alkil z jednym do dwóch atomów we- gla, a R2 i R3 sa takie same lub rózne i oznaczaja atom wodoru lub alkil z jednym do dwóch atomów wegla, lub R2 i R3 razem z atomem azotu tworza pierscien morfoliny lub piperazyny. Wzór 1 W zó r 2 W zó r 3 W z ó r 4 PL PL PL PL
Description
Wynalazek dotyczy nowych zwiqzków chemicznych, pochodnych genisteiny, które wykazujq wlasciwosci immunosupresyjne i przeciwnowotworowe. Genisteina (4',5,7-trójjiydroksyizoflawon), jest naturalnie wyst?pujqcym hormonem roslinnym - fitoestrogenem. Wiadomo, ze genisteina inhibituje specyficznie zarówno kinaz? proteinowq, jak i topoizomeraz? II DNA.
Znane jest francuskie zgloszenie patentowe o nr FR 2 693 724, w którym opisane sqO-alkilowe pochodne genisteiny.
Wynalazek dotyczy zwiqzków o wzorze ogólnym 1, w którym R1, R2, r3 sq takie same lub rózne, R1 oznacza atom wodoru lub alkil z jednym do dwóch atomów w?gla, a R2 i R3 sq takie same lub rózne i oznaczajqatom wodoru lub alkil z jednym do dwóch atomów w?gla, lub R2 i R3 razem z atomem azotu tworzq pierscieù morfoliny lub piperazyny.
Korzystny zwiqzek o wzorze 1 jest reprezentowany przez struktur? 2, w której R1, R2 i R3 sq identyczne i oznaczajq etyl.
Gdy R1 oznacza atom wodoru, a R2 i R3 razem z atomem azotu tworzq pierscieù morfoliny, wówczas korzystny zwiqzek o wzorze ogólnym 1 reprezentowany jest przez struktur? 3.
Gdy R1 oznacza atom wodoru, a R2i R3 razem z atomem azotu tworzq pierscieù piperazyny, to korzystny zwiqzek o wzorze ogólnym 1 reprezentowany jest przez struktur? 4.
Korzystne zwiqzki przedstawione sq wzorami:
- 4H-1-Benzopiran-4-on, 5,7-dihydroksy-3-(4-hydroksyfenyl), zwiqzek z trietyloaminq (1:1)-C2,H26NO5.
- 4H-1-Benzopiran-4-on, 5,7-dihydroksy-3-(4-hydroksyfenyl), zwiqzek z morfolinq (1:1)-C19H2oNO6.
- 4H-1-Benzopiran-4-on, 5,7-dihydroksy-3-(4-hydroksyfenyl), zwiqzek z piperazynq(1:1)-CI9H21N2°5.
Zwiqzki o wzorze ogólnym 1 wytwarza si?, wedlug wynalazku, w reakcji kompleksowania genisteiny z aminami w alkoholu i krystalizacj? powstalych soli amin.
Zwiqzki o wzorach 2, 3, 4 mogq wyst?powac w róznych formach, w zaleznosci od tego, która z grup fenolowych ulega jonizacji oraz stosunku stechiometrycznego genisteiny i aminy. Korzystnie stosunek ten wynosi 1:1, a jonizacji ulega grupa fenolowa w pozycji 7.
Stwierdzono, ze pochodne genisteiny, wedlug wynalazku, o wzorze ogólnym 1, korzystnie o wzorach 2, 3, 4 wykazujq, wedlug wynalazku, in vitro, dzialanie immunosupresyjne i przeciwnowotworowe udokumentowane testami.
179 170
Testy biologiczne. Stwierdzono ze, wedlug wynalazku, zwiqzki o wzorze ogólnym 1, korzystnie oznaczone wzorami 2, 3,4 hamujq ekspresj? markerów dyferencjacji i aktywacji limfocytów stymulowanych Conkanavalina-A.
Markery dyferencjacji i aktywacji na powierzchni limfocytów oznaczano w 72 godzinnych hodowlach komórkowych w obecnosci Con-A i immunosupresanta w st?zeniu 80 mm. Ilosc CD3, CD4, CD8, CD16+56, CD25, CD38, CD69, CD71 i HLA-DR pozytywnych limfocytów oznaczano uzywajqc FACScan. Uzyskane wyniki porównano z kontrolnymi hodowlami limfocytów otrzymanymi w tym samym czasie w obecnosci podloza hodowlanego i kontrolnymi hodowlami zawierajqcymi w podlozu tylko Con-A.
W hodowlach komórkowych zawierajqcych immunosupresant stwierdzono statystycznie istotny spadek ilosci aktywowanych limfocytów w porównaniu z hodowlami kontrolnymi bez immunosupresanta (p<0.001). Zaobserwowano spadek CD3, CD4, CD25, CD71 pozytywnych limfocytów (0.7 do 1.7 raza) i mniej CD2CD25, CD3CD71, CD4CD69, CD8CD38 pozytywnych limfocytów (0.6 do 2.5 raza odpowiednio, p<0.0007) porównujqc z kontrolnymi limfocytami Con-A stymulowanymi bez immunosupresanta. Zywotnosc limfocytów w obecnosci immunosupresantów i kontrolnych limfocytów byla taka sama i byla wicksza niz 95%.
Potencjalne zastosowanie zwiqzków, wedlug wynalazku, przedstawionych wzorem ogólnym 1, korzystnie o wzorach 2, 3 i 4:
I. Medycyna ludzka i weterynaryjna
- Allotransplantacja (w obrcbie tego samego gatunku)
- Xenotransplantacja (pomiedzy róznymi gatunkami)
- Leczenie chorób autoimmunologicznych
- Onkologia
II. Przemysl kosmetyczny
Przyklady otrzymywania oraz charakterystyka korzystnych zwiqzków o wzorach 2, 3, 4 podana jest ponizej.
Przyklad I.
Do zawiesiny genisteiny (500 mg, 1.85 mmol) w metanolu (10 ml) dodano trietyloamin? (3 ml) chlodzqc mieszanin? reakcyjnq wodq. Po 15 min. odparowano rozpuszczalnik i nadmiar trietyloaminy pod prózniq. Otrzymany produkt 2 suszono pod wysokq prózniq. Otrzymano sól genisteiny z trietyloaminq (2). Wydajnosc 680 mg.
IR (KBr): v=2454-3078 (br OH, NH), 1653 (C-O) cm-. Ή NMR (DMSO-d6): δ - 0.97 (t, 9H, J=7.1 Hz), 2.57 (q, 6H, J=7.1 Hz), 6,16 (d, 1H, J=2.0 Hz), 6.32 (d, 1H, J=2.0 Hz), 6.7816.82 (m, 2H, 1/2 AA'XX), 7.33 i 7.38 (m, 2H, 1/2 AA'XX'), 8.26 (s, 1H), 12.9 (br s, 1H).
13C NMR (CDC13 + DMSO-d6): 8 = 9.67, 44,69, 92.97, 98.52, 103.25, 114.17, 120.35, 121.71, 128.78, 151.24, 156.39, 156.81, 161.14, 164.76, 179.09.
Przyklad II.
Do zawiesiny genisteiny (305 mg, 1.13 mmol) w metanolu (4.5 ml) dodano po kropli morfolin? (1 ml) chlodzqc mieszanin? reakcyjnq wodq. Metanol i nadmiar morfoliny odparowano pod prózniq. Otrzymany produkt rozpuszczono w chloroformie z dodatkiem metanolu (ok. 5%) i wytrqcono sól heksanem. Otrzymano sól genisteiny z morfolinq(3). Po odsqczeniu suszono produkt 3 pod prózniq. Wydajnosc 285 mg.
IR (KBr): v= 2479-3398 (OH, NH), 1656 (C=O) cm 11 Ή NMR (CDCh, + DMSO-d6): 8 = 2.72 (m, 4H), 3.52 (m, 4H), 6.14 (d, 1H, J=2. 1 Hz), 6.25 (d, 1H, J=2. 1 Hz), 6.75 i 6.79 (m, 2H, 1/2 AA'XX'), 7.24 i 7.29 (m, 2H, 1/2 AA'XX'), 7.93 (s, 1H).
l3C NMR (CDCI3 + DMSO-d6): 8 = 45.28, 66,81, 93.20, 98.67, 104.15, 114.66, 120.73, 122.38, 129.18, 151.64, 156.75, 157.18, 161.62, 163.98, 179.75.
Przyklad III.
Do zawiesiny genisteiny (243 mg, 0.9 mmol) w metanolu (12 ml) dodano piperazyn? (77 mg, 0.9 mmol) i mieszanin? podgrzano do rozpuszczenia si? genisteiny. Roztwór odparowano na wyparce, a pozostalosc krystalizowano z mieszaniny chloroform - etanol (ok. 5:1). Otrzymano sól genisteiny z piperazynq (4). Wydajnosc produktu 4 wynosi 180 mg.
179 170
IR (KBr): v = 3440 (br OH), 3247-2581(br NH), 1657 (C=O) cm’ Ή NMR (CDCI3 + DMSO-d6): δ=2.71 (s, 8H), 6,14 (d, 1H, >2. 1 Hz), 6.24 (d, 1H, J=2.1 Hz), 6.75 i 6.79 (m, 2H, 1/2 AA'XX'), 7.22 i 7.27 (m, 2H, 1/2 AAXX), 7.84 (s, 1H).
13C NMR (CDCI3 + DMSO-d6): δ = 43.77, 92.76, 98.55, 101.53, 113.49, 119.89, 120.64, 128.28, 150.67, 155.88, 156.42, 160.42, 167.07, 178.00.
Widma ’H NMR (200 MHz) standaryzowano wg sygnalu DMSO (2.49 ppm), a widma 13C NMR wg sygnalu CDO3 (77.0 ppm). Podane wartosci integracji sygnalów sq przyblizone ze wzglydu na rózny sklad soli (stosunek genisteina - amina jest niezupelnie 1:1).
Claims (4)
1. Nowe zwiqzki, pochodne genisteiny, o wzorze ogólnym 1, w którym R1, R2, R3 sq takie same lub rózne, Ri oznacza atom wodoru lub alkil zjednym do dwóch atomów wegla, a R2 i R3 sq takie same lub rózne i oznaczajqatom wodoru lub alkil zjednym do dwóch atomów wegla, lub R2 i R3 razem z atomem azotu tworzq pierscieù morfoliny lub piperazyny.
2. Zwiqzek wedlug zastrz. 1, reprezentowany przez struktur? 2, jezeli we wzorze ogólnym 1, Ri, R2 i R3 sq identyczne i oznaczajq etyl.
3. Zwiqzek wedlug zastrz. 1, reprezentowany przez struktur? 3, jezeli we wzorze ogólnym 1, R1 oznacza atom wodoru, a R2 i R3 razem z atomem azotu tworzq pierscieù morfoliny.
4. Zwiqzek wedlug zastrz. 1, reprezentowany przez struktur? 4, jezeli we wzorze ogólnym 1, R1 oznacza atom wodoru, a R2i R3 razem z atomem azotu tworzq pierscieù piperazyny.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL95310486A PL179170B1 (pl) | 1995-09-15 | 1995-09-15 | Nowe zwiazki,pochodne genisteiny PL PL PL PL |
| US08/696,371 US5637703A (en) | 1995-09-15 | 1996-08-13 | Derivatives of genistein |
| JP8255372A JP2979469B2 (ja) | 1995-09-15 | 1996-09-06 | ゲニステイン新規誘導体 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL95310486A PL179170B1 (pl) | 1995-09-15 | 1995-09-15 | Nowe zwiazki,pochodne genisteiny PL PL PL PL |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL310486A1 PL310486A1 (en) | 1997-03-17 |
| PL179170B1 true PL179170B1 (pl) | 2000-07-31 |
Family
ID=20065904
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL95310486A PL179170B1 (pl) | 1995-09-15 | 1995-09-15 | Nowe zwiazki,pochodne genisteiny PL PL PL PL |
Country Status (3)
| Country | Link |
|---|---|
| US (1) | US5637703A (pl) |
| JP (1) | JP2979469B2 (pl) |
| PL (1) | PL179170B1 (pl) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6028099A (en) * | 1998-03-13 | 2000-02-22 | John Hopkins University, School Of Medicine | Use of an inhibitor of the protein tyrosine kinase pathway in the treatment of choroidal neovascularization |
| US5980929A (en) * | 1998-03-13 | 1999-11-09 | Johns Hopkins University, School Of Medicine | Use of a protein tyrosine kinase pathway inhibitor in the treatment of retinal ischmemia or ocular inflammation |
| US5919813C1 (en) * | 1998-03-13 | 2002-01-29 | Univ Johns Hopkins Med | Use of a protein tyrosine kinase pathway inhibitor in the treatment of diabetic retinopathy |
| US6399655B1 (en) | 1998-12-22 | 2002-06-04 | Johns Hopkins University, School Of Medicine | Method for the prophylactic treatment of cataracts |
| US20030232741A1 (en) * | 2002-05-06 | 2003-12-18 | Washington University | Methods of treatment of glaucoma and other conditions mediated by NOS-2 expression via inhibition of the EGFR pathway |
| CA2590048C (en) * | 2007-05-23 | 2013-07-16 | Institut National De La Recherche Scientifique | Cytosine nucleoside analogs and isoflavones and uses thereof |
| BRPI0923504A2 (pt) * | 2008-12-11 | 2020-05-26 | Axcentua Pharmaceuticals Ab | Formas cristalinas de genisteína. |
| US7863325B2 (en) * | 2008-12-11 | 2011-01-04 | Axcentua Pharmaceuticals Ab | Crystalline genistein sodium salt dihydrate |
| WO2011075592A1 (en) | 2009-12-17 | 2011-06-23 | Merial Limited | Compositions comprising macrocyclic lactone compounds and spirodioxepinoindoles |
| IL272246B1 (en) | 2017-07-28 | 2025-09-01 | Applied Therapeutics Inc | Derivatives of 2-(4-oxo/thioketone/azo-3-((substituted)benzo[d]thiazol-2-yl)methyl)- 3,4-dihydrothieno[3,4-d]pyridazin-1-yl)acetic acid for use as aldose reductase inhibitors in treating galactosemia or preventing complications associated with galactosemia |
| MX2022013658A (es) | 2020-05-01 | 2023-03-01 | Applied Therapeutics Inc | Inhibidores de la aldosa reductasa para tratar la deficiencia de sorbitol deshidrogenasa. |
| CN117447432A (zh) * | 2023-10-16 | 2024-01-26 | 中国海洋大学 | 一种具有cd38抑制活性的染料木素及其制备方法和应用 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3505611A1 (de) * | 1984-11-26 | 1986-05-28 | Merck Patent Gmbh, 6100 Darmstadt | Halogen-hydroxy-flavone |
-
1995
- 1995-09-15 PL PL95310486A patent/PL179170B1/pl unknown
-
1996
- 1996-08-13 US US08/696,371 patent/US5637703A/en not_active Expired - Fee Related
- 1996-09-06 JP JP8255372A patent/JP2979469B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| US5637703A (en) | 1997-06-10 |
| JP2979469B2 (ja) | 1999-11-15 |
| JPH09183774A (ja) | 1997-07-15 |
| PL310486A1 (en) | 1997-03-17 |
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