CS196618B1 - Derivatives of pyridine-4-carboxyhydrazide with potential antitubercular and antitumour actions and method for their preparing - Google Patents
Derivatives of pyridine-4-carboxyhydrazide with potential antitubercular and antitumour actions and method for their preparing Download PDFInfo
- Publication number
- CS196618B1 CS196618B1 CS462676A CS462676A CS196618B1 CS 196618 B1 CS196618 B1 CS 196618B1 CS 462676 A CS462676 A CS 462676A CS 462676 A CS462676 A CS 462676A CS 196618 B1 CS196618 B1 CS 196618B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- pyridine
- derivatives
- carboxhydrazide
- methoxyphenyl
- potential
- Prior art date
Links
- 230000002365 anti-tubercular Effects 0.000 title claims description 5
- 230000000259 anti-tumor effect Effects 0.000 title claims description 5
- 238000000034 method Methods 0.000 title claims description 4
- -1 ketone compounds Chemical class 0.000 claims description 14
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical class NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 125000000468 ketone group Chemical group 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 239000000126 substance Substances 0.000 description 7
- VXIXUWQIVKSKSA-UHFFFAOYSA-N 4-hydroxycoumarin Chemical compound C1=CC=CC2=C1OC(=O)C=C2O VXIXUWQIVKSKSA-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 2
- 241000186365 Mycobacterium fortuitum Species 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 239000001273 butane Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000004775 coumarins Chemical class 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 2
- 201000008827 tuberculosis Diseases 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000006290 2-hydroxybenzyl group Chemical group [H]OC1=C(C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 description 1
- CXOKVBPWTHFGTN-UHFFFAOYSA-N 3-[(2-hydroxyphenyl)methylidene]chromene-2,4-dione Chemical compound OC1=CC=CC=C1C=C1C(=O)C2=CC=CC=C2OC1=O CXOKVBPWTHFGTN-UHFFFAOYSA-N 0.000 description 1
- PJKDVDQLFSFEBL-UHFFFAOYSA-N 4-hydroxy-3-(3-oxo-1,3-diphenylpropyl)chromen-2-one Chemical compound O=C1OC=2C=CC=CC=2C(O)=C1C(C=1C=CC=CC=1)CC(=O)C1=CC=CC=C1 PJKDVDQLFSFEBL-UHFFFAOYSA-N 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- AFWKBSMFXWNGRE-ONEGZZNKSA-N Dehydrozingerone Chemical compound COC1=CC(\C=C\C(C)=O)=CC=C1O AFWKBSMFXWNGRE-ONEGZZNKSA-N 0.000 description 1
- 244000303040 Glycyrrhiza glabra Species 0.000 description 1
- 208000008342 Leukemia P388 Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N benzo-alpha-pyrone Natural products C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 230000003327 cancerostatic effect Effects 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- AFWKBSMFXWNGRE-UHFFFAOYSA-N dehydrozingerone Natural products COC1=CC(C=CC(C)=O)=CC=C1O AFWKBSMFXWNGRE-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960001005 tuberculin Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Vynález sa týká niektorých nových derivátov pýridín-4-karboxhydrazidu (INH) ako potenciálnych tuberkúlostatík a kancerostatík a spósobu ich přípravy.The present invention relates to certain novel pyridine-4-carboxhydrazide (INH) derivatives as potential tuberculin and cancerostatics, and to a process for their preparation.
Potenciálny protinádorový účinok niektorých derivátov INH sledoval J. P. Matvejčuk (Vopr. eksp. onkol. 3/1968/101) a zistil, že niektoré z nich inhibovali tvorbu tumorov. Pri hodnotení biologických účinkov inej skupiny derivátov INH Μ. I. Colnághi, G. Della Porte á L. Parmí (Tumóri 55/1969/ /309) zistili, že samotný INH nepotláča tvorbú hádorov, žatial’ čo L. D. Jones, D. G. pajrchild a W. C. Morse (Am. Rev, Resp. Dis., 103/1^71/612) potvrdili potenciálny karcinogénny účinpl^blpktorých derivátov INH. F. Lacour, G. Oberling a M. Guerin (Bull. Ass. Franc. Cancer 44/1957/88) zistili,. že antikoagulanciá typu kumarínu inhibovali rast niektorých nádorov u experimentálnych zvierat, pričom tieto látky znižujú tvorbu metastáz v prúcach a v pečeni zvierat, ako to potvrdili vo svojich prácach D. Agostino, E. E. Cliffton, A. Girolamo (Cancer 19/1966/284), M. Lawinski a spol· (Arch. Immunol. Ther. Exp.', 19/1971/532) azvyšujú šúčasné prežívanie pokusných zvierat, ako..udáš vajú vo svojich výsledkách S. Wood, E. D. Holyóke a ί. H. YardJey (Canad.Conf. Cancer 4/1961/223).The potential antitumor effect of some INH derivatives has been studied by J. P. Matvejchuk (Vopr. Eksp. Onkol. 3/1968/101) and found that some of them inhibited tumor formation. In assessing the biological effects of another class of INH derivatives Μ. I. Colnághi, G. Della Porte and L. Parmí (Tumors 55/1969 / / 309) found that INH alone did not suppress the formation of riddles, in particular LD Jones, DG pajrchild and WC Morse (Am. Rev, respectively. Dis. , 103/1 (71/612) confirmed the potential carcinogenic effect of certain INH derivatives. F. Lacour, G. Oberling and M. Guerin (Bull. Ass. Franc. Cancer 44/1957/88) found. that coumarin-type anticoagulants inhibited the growth of certain tumors in experimental animals, which reduce the formation of metastasis in the lungs and liver of animals, as confirmed by D. Agostino, E. Cliffton, A. Girolamo (Cancer 19/1966/284), M. Lawinski et al (Arch. Immunol. Ther. Exp. ', 19/1971/532) and enhance the survival of experimental animals as reported by S. Wood, ED Holyóke and ί. H. YardJey (Canad.Conf. Cancer 4/1961/223).
A. L. Cetlin a spol, (Tr. Bot. Inst. AN ZSSR 5, No. 16/1972/7) popísali cytotoxický účinok niektorých prírodných derivátov kumarínu na buňky nádorov, R. A.' Finnegan, Κ. E. Merkel a N. Back (J. Pharm. Sci. 61/19/2/1599) účinok syntetických kumarínov na S-180.A. L. Cetlin et al. (Tr. Bot. Inst. AN USSR 5, No. 16/1972/7) described the cytotoxic effect of some natural coumarin derivatives on tumor cells, R. A. ' Finnegan, Κ. E. Merkel and N. Back (J. Pharm. Sci. 61/19/2/1599) the effect of synthetic coumarins on S-180.
Lespagnol A. a spol. (Bull. Soc. Pharm. Lilie 1/1955/30), Η, H. Fox a J. T. Gibas (J. Org. Chem; 18/1953/983), P. P. T. Sah a S. A. Peoples (J. Am. Pharm. Áss,,i 43/1954/513). připravili deriváty, .pyridín-4-karboxhydrazidu so 4-fenyl-3-butén-27onom a mnohými ďalšími karbonylovými zlúčeninami, avšak tieto látky vykazovali v pokusech; iba malý. antituberkulózny efekt.Lespagnol A. et al. (Bull. Soc. Pharm. Lilie 1/1955/30), Fox, H. Fox and JT Gibas (J. Org. Chem; 18/1953/983), PPT Sah and SA Peoples (J. Am. Pharm. Ass. ,, i 43/1954/513). prepared derivatives of pyridine-4-carboxhydrazide with 4-phenyl-3-butene-27one and many other carbonyl compounds, but these have shown in experiments; only small. antituberculous effect.
Deriváty pyri^ín-4-karboxhydrazidu s potenciálnyrr^i antituberkulóznymi a potinádorovýml účinkami obecnéřro vzorca I kdeaR..je -a; .Pyridine-4-carboxhydrazide derivatives having the potential antituberculous and antitumor effects of the general formula I wherein R is -a; .
-R-R
R pričorti Rý znamená metyl alebo fenyl, R2 znamenáR pričorti R y is methyl or phenyl, R 2 is
-CH-GHCH-GH
19661 8 alebo19661 8 or
kde R3 znamená hydroxy alebo metoxy skupinu, alebowherein R 3 represents a hydroxy or methoxy group, or
R,- CH 0 Ί A JlrR, - CH 0 Ί A Jlr
kde R4 znamená hydroxyfenyl, alebo metoxyfenyl, sa pripravujú kondenzáciou pyridín-4-karboxhydrazidu s ketozlůčeninami obecného vzorca II kde Rt a R2 znamená to isté, ako už bolo uvedené, alebo s ketozlůčeninami obecného vzorca IIIwherein R 4 is hydroxyphenyl, or methoxyphenyl, are prepared by condensation of pyridine-4-carboxhydrazide with the ketone compounds of formula II wherein R 1 and R 2 are as previously described or with ketone compounds of formula III
kde R4 znamená hydroxyfenyl alebo metoxyfenyl, v prostředí polárného, alebo semipolárneho rozpúšťadla a výsledný produkt sa izoluje kryštalizáciou.wherein R 4 is hydroxyphenyl or methoxyphenyl, in a polar or semi-polar solvent medium, and the resulting product is isolated by crystallization.
Příklad 1Example 1
Příprava látky č. 1 4-(4-hydroxy-3-metoxyfenyl)-2-pyridín-4-karboxhydrazón-3-buténu j: ¾ ,Preparation of substance no. 1- 4- (4-hydroxy-3-methoxyphenyl) -2-pyridine-4-carboxhydrazone-3-butene j: ¾,
C17H17N3O6 m. v. 311,34 0,18 g (1,3 mM) pyridín-4-karboxhydrazidu (SPOFA, Praha) rozpuštěných v 2 ml 50% vodného etanolu sa přidalo k 0,25 g (1,3 mM) 4-(4-hydroxy-3-metoxyfenyl)-3-butén-2-ónu syntetizovaného z vanilínu a acetonu podl'a Mc Gookin A., Sinclair D. C. J. Chem, Soc., (1928/1170), v 2 ml 50% vodného etanolu. Zmes sa zahriala do varu a nechala krištalizovať. Látka sa prekryštalizovala z 50% vodného etanolu a vákuovo vysušila. Získalo sa 0,20 g (0,6 mM) 4-(4-hydroxy-3-metoxyfenyl)-2-pyridín-4-karboxhydrazón-3-buténu, b. t. 171 až 172,5 °C, UV Amax:C 17 H 17 N 3 O 6 mv 311.34 0.18 g (1.3 mM) pyridine-4-carboxhydrazide (SPOFA, Prague) dissolved in 2 ml of 50% aqueous ethanol was added to 0.25 g (1, 3 mM) 4- (4-hydroxy-3-methoxyphenyl) -3-buten-2-one synthesized from vanillin and acetone according to Mc Gookin A., Sinclair DCJ Chem, Soc., (1928/1170), at 2 ml of 50% aqueous ethanol. The mixture was heated to boiling and allowed to crystallize. The material was recrystallized from 50% aqueous ethanol and dried in vacuo. 0.20 g (0.6 mM) of 4- (4-hydroxy-3-methoxyphenyl) -2-pyridine-4-carboxhydrazone-3-butene was obtained, mp 171-172.5 ° C, UV max :
264 a 204 nm v etanole.264 and 204 nm in ethanol.
Příklad 2Example 2
Priprava látky č. 2 1,3-difenyl-1-(pyridín-4-karboxhydrazón)-2-propénuPreparation of substance no. 2 1,3-Diphenyl-1- (pyridine-4-carboxhydrazone) -2-propene
C21H17N3O m. v. 327,39 K 0,65 g (3,12 mM) 1,3-difenyl-2-propén-1-ónu připraveného z acetofenónu a benzaldehydu podl'a E. P. Kohler, Η. M. Chadwell., Org. Syntheses, Col. Vol, I, (1941/78) v 5 ml 2-propanolu sa přidalo 0,45 g (3,28 mM) pyridín-4-karboxhydrazidu (SPOFA, Praha) a zmes sa zahrievala do rozpustenia tuhých zložiek; na chladnom mieste vykrištalizovaná látka sa rekryštalizovala z 80% vodného etanolu. Získalo sa 0,50 g (1,5mM) 1,3-d ifenyl-1 -(pyridín-4-karboxhydrazón)-2-propénu, b. t. 141 až 142°C, UVAmax: 240 a 204 nm v etanole, IČ: 3400, 3300, 2950, 1680, 1590, 1540, 1490, 1450, 1400, 1360, 1280, 1050, 980, 820 cm'1 v chloroforme.C 21 H 17 N 3 O m v 327.39 To 0.65 g (3.12 mM) of 1,3-diphenyl-2-propen-1-one prepared from acetophenone and benzaldehyde according to EP Kohler, ref. M. Chadwell., Org. Syntheses, Col. Vol, I, (1941/78) in 5 ml of 2-propanol was added 0.45 g (3.28 mM) of pyridine-4-carboxhydrazide (SPOFA, Prague) and the mixture was heated to dissolve the solids; The cold crystallized material was recrystallized from 80% aqueous ethanol. 0.50 g (1.5 mM) of 1,3-diphenyl-1- (pyridine-4-carboxhydrazone) -2-propene was obtained, mp 141-142 ° C, UVA max : 240 and 204 nm in ethanol, IR : 3400, 3300, 2950, 1680, 1590, 1540, 1490, 1450, 1400, 1360, 1280, 1050, 980, 820 cm -1 in chloroform.
Příklad 3Example 3
Priprava látky č. 3 1,3-difenyl-1-(pyridín-4-karboxhydrazón)-3-(4-hydroxykumarin-3-yl)-propánuPreparation of substance no. 1,3-Diphenyl-1- (pyridine-4-carboxhydrazone) -3- (4-hydroxycoumarin-3-yl) -propane
C30H23N3O4 m. v. 441,54 0,9 g (2,42 mM) 1,3-difenyl-1-(4-hydroxykumarin-3-yl)-propán-3-ónu (získaný reakciou 4-hydroxykumarínu s 1,3-difenyl-2-propén-1-ónu, Ikawa M., a spol., J. Am. Chem. Soc., 66 (1944/902) v 5 ml 2-propanolu sa zmiešalo s 0,34 g (2,5 mM) pyridín-4-karboxhydrazidu (SPOFA, Praha) a zahriala sa do rozpustenia tuhých častíc. Zmes sa nechala kryštalizovať a vylúčené kryštály (0,11 g) nezreagovaného pyridín-4-karboxhydrazidu sa odsáli. Z matečného luhu sa vákuovo oddestilovalo rozpúšťadlo a zbytok sa trikrát rekryštalizoval z 94% etanolu. Po vysušení sa získalo 0,62 g (1,40 mM) 1,3-difenyl-1-(pyridín-4-karboxhydrazón)-3-(4-hydroxykumarin-3-yl)-propánu, b. t. 139 až 141 °C, UVAmax 303, 289, 239, 207 nm v etanole, IČ: 3700. 3300, 2990, 1690, 1610, 1550, 1480, 1450, 1400, 1370, 1310, 1250, 1190, 1060, 920 cm1 v chloroforme.C 30 H 23 N 3 O 4 mv 441.54 0.9 g (2.42 mM) 1,3-diphenyl-1- (4-hydroxycoumarin-3-yl) -propan-3-one (obtained by reaction of 4- hydroxycoumarin with 1,3-diphenyl-2-propen-1-one, Ikawa M., et al., J. Am. Chem. Soc., 66 (1944/902) in 5 ml of 2-propanol was mixed with 0, 34 g (2.5 mM) of pyridine-4-carboxhydrazide (SPOFA, Prague) was heated to dissolve the solids, the mixture was allowed to crystallize and the precipitated crystals (0.11 g) of unreacted pyridine-4-carboxhydrazide were filtered off with suction. The solvent was distilled off in vacuo and the residue was recrystallized three times from 94% ethanol to give 0.62 g (1.40 mM) of 1,3-diphenyl-1- (pyridine-4-carboxhydrazone) -3- (4- hydroxycoumarin-3-yl) -propane, mp 139-141 ° C, UVA max 303, 289, 239, 207 nm in ethanol, IR: 3700, 3300, 2990, 1690, 1610, 1550, 1480, 1450, 1400, 1370 , 1310, 1250, 1190, 1060, 920 cm -1 in chloroform.
Příklad 4Example 4
Priprava Jatky č. 4 1-(4-hydroxy-3-metoxyfenyl)-1- (4 -hyplroxykumarin-3-yl) -3- (pyridín-4-karboxhydrazónj-butánuPreparations Slaughterhouses no. 4- 1- (4-Hydroxy-3-methoxyphenyl) -1- (4-hydroxycoumarin-3-yl) -3- (pyridine-4-carboxhydrazone) butane
C26H23N3O6 m. v. 473,48 , 2,0 g (6i,4 mM) 3-Jl-^-hydřoxy-S-metoxyfenyO-S-oxobutylJ-4-hydroxykumarínu (získaný reakciou 1(-4-hydroxy-3-metoxyfenyl)-3-oxobuténu-1 s 4-hydroxykumarínu, Ikawa M., a spol., J. Am. Chem. Soc., 66 (1944/902) a 0,88 g (6,4 mM) pyridín-4-karboxhydrazidu (SPOFA, Praha) sa zahrievalo v 15 ml dioxánu do úplného rozpustenia. Po vychladnutí z roztoku vypadávajú kryštály, ktoré po 2násobnej rekryštalizácii z 2-propanolu poskytliC 2 6H 23 N 3 O 6 mv 473.48, 2.0 g (6i, 4 mM) of 3-β-hydroxy-5-methoxyphenyl-5-oxobutyl-4-hydroxycoumarin (obtained by reaction 1 (-4- hydroxy-3-methoxyphenyl) -3-oxobutene-1 with 4-hydroxycoumarin, Ikawa M., et al., J. Am. Chem. Soc., 66 (1944/902) and 0.88 g (6.4 mM ) of pyridine-4-carboxhydrazide (SPOFA, Prague) was heated in 15 ml of dioxane until complete dissolution.After cooling, crystals precipitated from the solution, which after recrystallization from 2-propanol twice gave
1,8 g (3,6 mM) 1-(4-hydroxy-3-metoxyfenyl)-1-(4-hydroxykumarin-3-yl) - 3 - (pyridin - 4 -karboxhydrazón)-butánu, b. t.. 208 až 209 °C, UVAmax 345, 250 a 204 nm v metanole, IČ: 3700, 3550, 3000, 1680, 1660, 1630, 1595, 1500, 1410, 1360, 1250, 950 cm1 v chloroforme.1.8 g (3.6 mM) of 1- (4-hydroxy-3-methoxyphenyl) -1- (4-hydroxycoumarin-3-yl) -3- (pyridine-4-carboxhydrazone) butane, m.p. 208 DEG-209 DEG C., UVA max 345, 250 and 204 nm in methanol, IR: 3700, 3550, 3000, 1680, 1660, 1630, 1595, 1500, 1410, 1360, 1250, 950 cm @ -1 in chloroform.
966 1 8965 1 8
P r í k I a d 5EXAMPLE 5
Příprava látky č. 5 3-(2-hydroxybenzal)-4-(pyridín-4-karboxhydrazón)-2-oxochromanuPreparation of substance no. 5 3- (2-Hydroxybenzal) -4- (pyridine-4-carboxhydrazone) -2-oxochroman
C22H15N3O4 m. v. 385,39 Zmes 0,50 g (1,8 mM) 3-(2-hydroxybenzal)-2,4-diketochromanu (syntetizovaný z 4-hydroxykumarínu a salicylaldehydu, Sullivan W. R., a spol., J. Am. Chem. Soc., 65 (1943/2288) a 0,25 g (1,8 mM) pyridín-4-karboxhydrazidu sa zahrievalo v 6 ml 2-propanolu do rozpustenia zložiek. Na chladnom mieste vykríštalizovala látka, ktorá po trojnásobnej rekryštalizácii z 2-propanolu poskytla 0,22 g (0,5 mM) 3-(2-hydroxybenzal)-4-pyrldín-4-karboxhydrazón-2-oxochromanu, b. t. 243 až 245 °C, UVAma'x: 334, 296, 288, 238, 214 nm v metanole. Potenciálny protinádorový účinok bol hodnotený na základe inhibície značkovaných prekurzorov do buniek Ehrlichov ascitový karcinom a Leukémia P-388 in vitro metodou, ktorú popísali J. Fuška a spol. (Neoplasma 18/1971/631), antituberkulózny účinok bol hodnotený na dva kmene TBC: Myobacterium tuberculosis BCG a Mycobacterium fortuitum.C22H15N3O4 mv 385.39 A mixture of 0.50 g (1.8 mM) of 3- (2-hydroxybenzal) -2,4-diketochroman (synthesized from 4-hydroxycoumarin and salicylaldehyde, Sullivan WR, et al., J. Am. Chem. Soc., 65 (1943/2288) and 0.25 g (1.8 mM) of pyridine-4-carboxhydrazide were heated in 6 ml of 2-propanol to dissolve the components. propanol afforded 0.22 g (0.5 mM) of 3- (2-hydroxybenzyl) -4--pyridine-4-karboxhydrazón-2-oxochromanu, mp 243-245 DEG C., UVA has "x: 334, 296, 288 The potential antitumor effect was assessed by inhibiting the labeled precursors into Ehrlich's ascites carcinoma cells and Leukemia P-388 in vitro by the method described by J. Fuška et al (Neoplasma 18/1971/631), antituberculous the effect was evaluated on two strains of TB: Myobacterium tuberculosis BCG and Mycobacterium fortuitum.
Účinok niektorých látok na jednotlivé modely je uvedený v tabuTke 1.The effect of some substances on each model is shown in Table 1.
9661896618
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS462676A CS196618B1 (en) | 1976-07-13 | 1976-07-13 | Derivatives of pyridine-4-carboxyhydrazide with potential antitubercular and antitumour actions and method for their preparing |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS462676A CS196618B1 (en) | 1976-07-13 | 1976-07-13 | Derivatives of pyridine-4-carboxyhydrazide with potential antitubercular and antitumour actions and method for their preparing |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS196618B1 true CS196618B1 (en) | 1980-03-31 |
Family
ID=5389467
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS462676A CS196618B1 (en) | 1976-07-13 | 1976-07-13 | Derivatives of pyridine-4-carboxyhydrazide with potential antitubercular and antitumour actions and method for their preparing |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS196618B1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103601711B (en) * | 2013-11-04 | 2016-09-07 | 广东中烟工业有限责任公司 | A kind of coumarin derivative and its preparation method and application |
-
1976
- 1976-07-13 CS CS462676A patent/CS196618B1/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103601711B (en) * | 2013-11-04 | 2016-09-07 | 广东中烟工业有限责任公司 | A kind of coumarin derivative and its preparation method and application |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0861223B1 (en) | Process for the synthesis of curcumin-related compounds | |
| JPH0772164B2 (en) | New acrylic acid amides | |
| EP0220518A2 (en) | Preparation of substituted and disubstituted pyridine-2,3-dicarboxylate esters | |
| Aksenov et al. | Unexpected cyclization of ortho-nitrochalcones into 2-alkylideneindolin-3-ones | |
| Krapcho et al. | Bicyclic pyrazolines, potential central nervous system depressants and antiinflammatory agents | |
| Estevez et al. | Pyridazines. XV. Synthesis of 6‐aryl‐5‐amino‐3 (2H)‐pyridazinones as potential platelet aggregation inhibitors | |
| Gul et al. | Syntheses and stability studies of some Mannich bases of acetophenones and evaluation of their cytotoxicity against Jurkat cells | |
| Jiang et al. | Synthesis and evaluation of the antitumor activity of 2-amino-4-tetrahydroindazole-substituted benzamide derivatives as HSP90 inhibitors | |
| CS196618B1 (en) | Derivatives of pyridine-4-carboxyhydrazide with potential antitubercular and antitumour actions and method for their preparing | |
| Özdemir et al. | Synthesis of New 6-[4-(2-Fluorophenylpiperazine-1-YL)]-3 (2H)-Pyridazinone-2-Acethyl-2-(Substitutedbenzal) Hydrazone Derivatives and Evulation of Their Cytotoxic Effects in Liver and Colon Cancer Cell Lines | |
| Hussain et al. | A one‐step synthesis of 2‐methylthio‐6‐oxopyrimidine derivatives: preparation of fused pyrimidinones | |
| Cowden et al. | Flavins as potential antimalarials. 2. 3-Methyl-10-(substituted-phenyl) flavins | |
| Bijev | Synthesis and preliminary screening of carbohydrazides and hydrazones of pyrrole derivatives as potential tuberculostatics | |
| SU428602A3 (en) | METHOD OF OBTAINING BASIC-SUBSTITUTE DERIVATIVES 1 | |
| US4038415A (en) | Prostaglandin dehydrogenase inhibiting agents | |
| US3825535A (en) | Hydrazines,hydrazides and hydrazones of isoxazolopyridine carboxylic acids and esters | |
| US4085102A (en) | 2-Amino-8-arylideno-3,4,5,6,7,8-hexahydro-4-arlypyrido[4,3-d]pyrimidines | |
| Nosova et al. | Synthesis and Biological Activity of 2-Aryl-4-hydroxy-4-methyl-6-oxocyclohexane-1, 3-dicarboxamides | |
| Ratemi et al. | Pyridine and pyrimidine ring syntheses from 4‐(4‐morpholino)‐3‐pentenone and from ethyl 3‐(4‐morpholino)‐2‐butenoate | |
| US4254286A (en) | Benzaldehyde compounds | |
| JPS60246377A (en) | Composition containing novel heterocyclic compound | |
| CS232703B2 (en) | Production method of new quinoxaline-1,4-dioxide derivatives | |
| Wiley et al. | 2-Pyrones. X. 1 The Chemistry of Isodehydroacetic Acid Derivatives. A Hydrazine Degradation, Di-and Dialkylaminoethyl Esters and Anilides | |
| RU2049090C1 (en) | 7-acetyl-6-methoxy-3-methyl-1-phenyl-1h-1,2-diazaphenalene showing hypotensive activity | |
| Amr et al. | Synthesis and Antimicrobial Activity of Novel N 3, N 5-Bis [1-({1-[2-((E)-benzylidene) hydrazinyl]-1-oxo-3-phenylpropan-2-yl} amino)-3-methyl-1-oxobutan-2-yl] pyridine-3, 5-dicarboxamides |