6. Cinnolines and other heterocyclic types in relation to the chemotherapy of trypanosomiasis. Part XI. Some reactions of simple quinoxaline derivatives

Atkinson, C. M.; Brown, C. W.; Simpson, Jean

doi:10.1039/jr9560000026

Cited by 14 publications

(18 citation statements)

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“…11 Each was converted, without further purification, to 2-chloronitroquinoxalines (18b and d). Reduction of readily accessible 19 with tin and HCl, followed by oxidation, as described by Atkinson,12 provided a facile preparation of 7-amino-2-quinoxalinol (20). Alternatively, the latter was also obtained by direct reduction of 18c.…”

Section: Chemistrymentioning

confidence: 99%

“…A mixture of 20 12 (0.16 g, 1.0 mmol) and HCl (3 mL) was stirred together overnight before cooling to 0 °C. A cold solution of NaNO2 (0.08 g, 1.2 mmol) in water (2 mL) was added dropwise, and the mixture was stirred an additional 1 h. NaN3 (0.07 g, 1.1 mmol) in water (2 mL) was added, and the mixture was allowed to warm to room temperature.…”

Section: -Azido-2-chloroquinoxaline (21)mentioning

confidence: 99%

“…Pure material (0.31 g, 69% yield) was obtained after chromatography (4:1 hexanes:AcOEt) and recrystallization from EtOH-heptane to give white crystals: mp 111-112 °C; 1 H NMR (300 MHz, CDCl3) δ 8.76 (s, 1 H), 7.73-7.65 (m, 2 H), 7.56 (t, J ) 7.8 Hz, 1 H), 7.23-7.16 (m, 2 H), 6.99-6.91 (m, 2 H), 4.79 (q, J ) 6.9 Hz, 1 H), 3.79 (s, 3 H), 1.65 (d, J ) 6.6 Hz, 3 H); 13 C NMR (75 MHz, CDCl3) δ 172. 4, 157.5, 155.1, 146.6, 141.2, 139.4, 136.2, 132.9, 130.1, 127.5, 126.7, 122.4, 116.1, 73.1, 52.3, 18.6; IR (KBr) 1740 (CdO) cm -1 ; MS (EI) m/z (%) 358 (M + , 27), 299 (19), 243 (12), 163 (10), 149 (16), 137 (18), 123 (9), 121 (9), 109 (9), 107 (6), 97 (9), 95 (15), 93 (8), 85 (7), 83 (12), 81 (51), 73 (9), 71 (13), 69 (100), 67 (11), 60 (7). Anal.…”

Section: -{4-[(5-chloro-2-quinoxalinyl)oxy]phenoxy}propionic Acid (26a)mentioning

confidence: 99%

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Design, Synthesis, and Biological Evaluation of Analogues of the Antitumor Agent, 2-{4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy}propionic Acid (XK469)

et al. 2001

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2-(4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy)propionic acid (XK469) is among the most highly and broadly active antitumor agents to have been evaluated in our laboratories and is currently scheduled to enter clinical trials in 2001. The mechanism or mechanisms of action of XK469 remain to be elaborated. Accordingly, an effort was initiated to establish a pharmacophore hypothesis to delineate the requirements of the active site, via a comprehensive program of synthesis of analogues of XK469 and evaluation of the effects of structural modification(s) on solid tumor activity. The strategy formulated chose to dissect the two-dimensional parent structure into three regions-I, ring A of quinoxaline; II, the hydroquinone connector linkage; and III, the lactic acid moiety-to determine the resultant in vitro and in vivo effects of chemical alterations in each region. Neither the A-ring unsubstituted nor the B-ring 3-chloro-regioisomer of XK469 showed antitumor activity. The modulating antitumor effect(s) of substituents of differing electronegativities, located at the several sites comprising the A-ring of region I, were next ascertained. Thus, a halogen substituent, located at the 7-position of a 2-(4-[(2-quinoxalinyl)oxy]phenoxy)propionic acid, generated the most highly and broadly active antitumor agents. A methyl, methoxy, or an azido substituent at this site generated a much less active structure, whereas 5-, 6-, 8-chloro-, 6-, 7-nitro, and 7-amino derivatives all proved to be essentially inactive. When the connector linkage (region II) of 1 was changed from that of a hydroquinone to either a resorcinol or a catechol derivative, all antitumor activity was lost. Of the carboxylic acid derivatives of XK469 (region III), i.e., CONH2, CONHCH3, CON(CH3)2, CONHOH, CONHNH2, CN, or CN4H (tetrazole), only the monomethyl- and N,N-dimethylamides proved to be active.

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Section: Chemistrymentioning

confidence: 99%

Section: -Azido-2-chloroquinoxaline (21)mentioning

confidence: 99%

Section: -{4-[(5-chloro-2-quinoxalinyl)oxy]phenoxy}propionic Acid (26a)mentioning

confidence: 99%

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Design, Synthesis, and Biological Evaluation of Analogues of the Antitumor Agent, 2-{4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy}propionic Acid (XK469)

et al. 2001

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“…The product was purified by dissolving in 10 % NaOH solution (125 mL), treated with charcoal and then precipitated by addition of dilute HCl to give the title compound. Yield 11.4 g, 78 %, mp 268-269mC (Atkenson et al (1956) : 267-269mC).…”

Section: -Hydroxyquinoxaline (3)mentioning

confidence: 99%

Synthesis of new arylaminoquinoxalines and their antimalarial activity in mice

Rangisetty

Gupta

Prasad

et al. 2001

Journal of Pharmacy and Pharmacology

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2-Arylaminoquinoxalines were prepared by the condensation of 2-chloroquinoxaline with the appropriate Mannich bases in the presence of HCl. To synthesize the Mannich bases, 4-acetamidophenol was reacted with formaldehyde and dialkylamine to yield 3-[(dialkylamino) methyl]-4-hydroxyacetanilide, followed by hydrolysis. Antimalarial activities of the new arylaminoquinoxalines were evaluated against the rodent malaria parasite Plasmodium yoelii at a dose of 75 mg kg(-1). Three compounds synthesized (2-[3-[(diethylamino) methyl]-4-hydroxyanilino]-quinoxaline dihydrochloride (2b), 2-[3-[(pyrrolidinyl) methyl]-4-hydroxyanilino]-quinoxaline dihydrochloride (2f), and 2-[3-[(piperidinyl) methyl]-4-hydroxyanilino]-quinoxaline dihydrochloride (2g)) showed moderate antimalarial activity.

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“…It was reported that the reaction of 1,2-diaminoaromatic compound 1 with 1,2-dicarbonyl compounds 2 or 3 afforded the quinoxaline or pyrazin-2(1H)-one derivatives 4 and 5 [1,2]. However, condensation of 1,8-diaminonaphthalene with benzil 2 or alkyl carboxylate derivative of 3-furanone 7 furnished the perimidine derivatives 8 and 9, respectively [3][4][5] (Schemes 1 and 2).…”

Section: Introductionmentioning

confidence: 99%

Confirmed Mechanism for 1,8-Diaminonaphthalene and Ethyl Aroylpyrovate Derivatives Reaction, DFT/B3LYP, and Antimicrobial Activity of the Products

Abu‐Melha

2018

Journal of Chemistry

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Two new series of perimidine derivatives were prepared from the reaction of 1,8-diaminonaphthalene with ethyl aroylpyrovate followed by coupling for the products. The structures, the mechanism, and the tautomeric forms of the products have been discussed on the basis of spectral data aided with the computational study. Applying Guassian09 software, the reaction mechanism was assured. The energy contents were computed after optimization for all proposed structures. The likely extracted compound has a reduced heat during formation and internal energy which coincides with experimental outcomes. The antimicrobial activity of all products was screened, and their results indicated the presence of five derivatives more potent than the reference drugs used. The simulation procedure was executed by Autodock 4.2 tools over the expected compounds yielded (12 and 21). This computational technique asserts on the drug behavior inside the causative organism proteins. The organisms here match with that used in the antimicrobial and antifungal study.

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6. Cinnolines and other heterocyclic types in relation to the chemotherapy of trypanosomiasis. Part XI. Some reactions of simple quinoxaline derivatives

Cited by 14 publications

References 0 publications

Design, Synthesis, and Biological Evaluation of Analogues of the Antitumor Agent, 2-{4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy}propionic Acid (XK469)

Design, Synthesis, and Biological Evaluation of Analogues of the Antitumor Agent, 2-{4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy}propionic Acid (XK469)

Synthesis of new arylaminoquinoxalines and their antimalarial activity in mice

Confirmed Mechanism for 1,8-Diaminonaphthalene and Ethyl Aroylpyrovate Derivatives Reaction, DFT/B3LYP, and Antimicrobial Activity of the Products

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