CS211851B1 - Derivatives of the 7,8 dihydro-5h-izoindolo-/1,2-b/3/benzazepine-5- - Google Patents
Derivatives of the 7,8 dihydro-5h-izoindolo-/1,2-b/3/benzazepine-5- Download PDFInfo
- Publication number
- CS211851B1 CS211851B1 CS235479A CS235479A CS211851B1 CS 211851 B1 CS211851 B1 CS 211851B1 CS 235479 A CS235479 A CS 235479A CS 235479 A CS235479 A CS 235479A CS 211851 B1 CS211851 B1 CS 211851B1
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- Czechoslovakia
- Prior art keywords
- dihydro
- formula
- izoindolo
- benzazepine
- derivatives
- Prior art date
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- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 4
- WWVGXWRJWMUFSY-UHFFFAOYSA-N 1-benzazepin-5-one Chemical class O=C1C=CC=NC2=CC=CC=C12 WWVGXWRJWMUFSY-UHFFFAOYSA-N 0.000 claims description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 150000001204 N-oxides Chemical class 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- IQFYYKKMVGJFEH-OYDXRQHMSA-N 1-[(2r,4s,5s)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H]([14CH2]O)[C@@H](O)C1 IQFYYKKMVGJFEH-OYDXRQHMSA-N 0.000 description 1
- KCOKVCKMOZEQMO-UHFFFAOYSA-N 3-benzazepin-1-one Chemical group O=C1C=NC=CC2=CC=CC=C12 KCOKVCKMOZEQMO-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 239000008896 Opium Substances 0.000 description 1
- XXNNKVDBGXCFHP-HBFSDRIKSA-N Papaverrubine A Natural products O(C)[C@H]1O[C@@H]2[C@H](NCCc3c2cc2OCOc2c3)c2c1c1OCOc1cc2 XXNNKVDBGXCFHP-HBFSDRIKSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000003327 cancerostatic effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000004081 narcotic agent Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
POPIS VYNÁLEZU
K AUTORSKÉMU OSVEDČENIU ČESKOSLOVENSKASOCIALISTICKÁREPUBLIKA( 19 ) 211 851 <n> (Bl)
(61) (23) Výstavná priorita(22) Přihlášené 06 04 79(21) pV 2354-79 (51) Int. Cl? C 07 D 491/147// C 07 D 223/16 A 61 K 31/33
ÚŘAD PRO VYNÁLEZY
A OBJEVY (40) Zverejnené 31 07 81 (45) Vydané 01 12 83 (75)
Autor vynálezu PROKSA BOHUMIL ing.CSc., HLOHOVECVOTICKÍ ZDENO dr.ing.CSc.
PUSKA JÁN' ing.CSc., BRATISLAVA (54) Derivát 7,8-dihydro-5H-izoindolo-[l,2-bJ PO benzazepin-5-ónu 1
Vynález sa týká derivátu 7,8-dihydro-5H-iziončolo-[Í,2-b3(3jbenzazepin-5“ónu vzorea I;
vynález sa takisto týká spSsobu výroby derivátu vzorea I Látka vzorea I, ktorá doteraz nebola popísáná, je cennou, Yarmalogicky významnou látkous kancerostetickými účinkami.
Zlúčeniny základného skeletu 7,8-dihydro-5H-izoindolo-[l,2-l3j [3]benzazepin-5-ónu boli získané například oxidáeiou papaverrubínu A /Walterová, Šantavý, Coll.Czech.Cem. Commun. 33, 1623(1968), izoláciou zo zmesi vedíajáích opiových alkaloidov (Trojánek a sp., Coll.Czech.Cem.Commun. 40, 681, 1975), alebo syntézou vychádzajúcou z narkotik (Teitel a sp., Can.J.Chem. 50,2022, L972). Zlúčeninu uvedeného základného skeletu substituovaná v polohe 7 sa doteraz nepodá 211 851
Claims (2)
- 211 851 rilo pripravií. Při spSaobe výroby/ derivátu vzorce 1 sa podlá vynálezu postupuje tak, že aa najprv (Z)-nar-ceinimid oxidáciou, například peroxidem vodíka, prevedie na (Z)-narceinimid-N-oxid, ktorý sa po-tom cyklizuje dčinkom acyladnýeh činidel, například acetanhydridu, za teploty 40 až 70 °C. Kancerostatické vlastnosti látky vzorca I sa hodnotili metodou podía Fuškovej a sp. (Neo-plasma 24, 239, 1977). Pri koncentrácii 15-25 /ig/ml látky I dochádza k inhibícii inkorporácie14C adeninu 19,2 %, 14C valínu 7,4 %, 14C-tymidínu 18,6 %, l4C uridínu 78,9 % do nádorových bu-niek leukémie P-388. Bližšie podrobnosti vyplývájú z příkladu pravedenia. Příklad 1 7,8-dihydro-3,4,12-trimetoxy-7-dimetylamíno-10,ll-metyléndioxy-5H-izoindolo^l,2-bJ7 £3jbenzazepin-5-ón Roztok 5 g (Z)-narceinimidu v 25 ml acetonu sa zmleša s 4,5 ml 30 %-ného roztoku peroxidu vodí-ka a zmes sa refluxuje 1 hodinu ná vodnom kúpeli. Po 5 h sa přidá SalSích 100 ml acetonu, vylú-čená krystalická látka sa odfiltruje, premyje acetónom a vysuSí. Získajú sa 3,4 g (67 % teorie)(Z)-narceinimid-N-oxidu s t.t. 158-159 °C. 0,6 g tejto látky sa rozpustí v 5 ml acetanhydridu,zmes sa zahřeje na 50 °C a nechá voíne vychladnúi. Po 2 hodinách sa k ochladenej zmesi pomalypřidává 5 %-ný roztok hydroxidu draselného do hodnoty pH 7 a potom sa prídavkom 5 %-ného roztokuamoniaku upraví pH na hodnotu 9· Vylúčená látka sa odfiltruje a z vodného roztoku sa jej zvySokextrahuje 3 x po 25 ml chloroformu. Odpařením rozpúšíadla sa získaný odparok přidá k podielu zozrážania. Celkový výiažok 0.32 g oražovej látky, ktorá rekryštalizáciou z etanolu poskytne žia-daný produkt vo formě žitých kryštálov s t.t. 220-222 °C. PŘED MET VYNÁLEZU 1. Derivát 7,8-diohydro-5H-izoindolo£l,2-bJ[pJbenzazepin-5-ónu vzorce I(V
- 2. SpSsob výroby derivátu 7,8-dihydro-5H-izoindolo^í,2-bJ|3J“benzazepin-5-ónu vzorca I pod-ía bodu 1 vyznačujdci sa tým, že sa najprv (Z)-narceinimid oxidáciou, například peroxidom vodíka,prevádza na (Z)-narceinimid-N-oxid, ktorý sa potom cyklizuje údinkom acyladnýeh dinidiel, napří-klad anhydridu kyseliny octovéj, za teploty 40 až 70 °C.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS235479A CS211851B1 (en) | 1979-04-06 | 1979-04-06 | Derivatives of the 7,8 dihydro-5h-izoindolo-/1,2-b/3/benzazepine-5- |
| CS802885A CS211852B1 (en) | 1979-04-06 | 1980-04-24 | Derivative of the 5h-izoindolo/1,2-b/3/benzazepin-5-one |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS235479A CS211851B1 (en) | 1979-04-06 | 1979-04-06 | Derivatives of the 7,8 dihydro-5h-izoindolo-/1,2-b/3/benzazepine-5- |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS211851B1 true CS211851B1 (en) | 1982-02-26 |
Family
ID=5360441
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS235479A CS211851B1 (en) | 1979-04-06 | 1979-04-06 | Derivatives of the 7,8 dihydro-5h-izoindolo-/1,2-b/3/benzazepine-5- |
| CS802885A CS211852B1 (en) | 1979-04-06 | 1980-04-24 | Derivative of the 5h-izoindolo/1,2-b/3/benzazepin-5-one |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS802885A CS211852B1 (en) | 1979-04-06 | 1980-04-24 | Derivative of the 5h-izoindolo/1,2-b/3/benzazepin-5-one |
Country Status (1)
| Country | Link |
|---|---|
| CS (2) | CS211851B1 (cs) |
-
1979
- 1979-04-06 CS CS235479A patent/CS211851B1/cs unknown
-
1980
- 1980-04-24 CS CS802885A patent/CS211852B1/cs unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CS211852B1 (en) | 1982-02-26 |
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