- Novel molecular targeting anti-tumor aza-steroid derivative based on lipid toxicity and preparation and application thereof
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The invention provides a novel molecular targeting anti-tumor aza-steroid derivative based on lipid toxicity and a preparation method and application thereof, and belongs to the field of chemical medicines. The derivative is a compound as shown in a formula I, or a salt thereof, or a stereoisomer thereof. The compound is low in toxicity or basically non-toxic to normal cells, has an obvious inhibition effect to tumor cell lines, particularly has good lipid toxicity selectivity to tumor cells such as liver cancer, lung cancer and the like in vivo, and has an obvious inhibition effect; meanwhile, the compound can effectively activate SREBP1 and PPAR gamma, inhibit lipid transport MTTP, cause lipid aggregation in tumor cells and cause lipid toxicity of the tumor cells. The compound can be used for treating liver cancer, lung cancer and the like in a molecular targeting manner, is low in toxicity or even non-toxic, and has a good application prospect.
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Paragraph 0178; 0180; 0192; 0205; 0224
(2021/08/19)
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- A One-pot Facile Synthesis of 2,3-Dihydroxyquinoxaline and 2,3-Dichloroquinoxaline Derivatives Using Silica Gel as an Efficient Catalyst
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An efficient one-pot reaction has been developed for the synthesis of 2,3-dichloroquinoxaline derivatives 3a–n. The reaction was performed in two steps via a silica gel catalyzed tandem process from o-phenylenediamine and oxalic acid, followed by addition of phosphorus oxychloride (POCl3). A variety of 2,3-dichloroquinoxalines have been obtained in good to excellent overall yields. Eight known compounds 3a–3h were characterized by IR, 1H-NMR, and mass spectroscopies. Compounds 3i–3n without spectroscopic data were characterized by IR, 1H-NMR, 13C-NMR, and mass spectroscopies.
- Zhang, Pei-Ming,Li, Yao-Wei,Zhou, Jing,Gan, Lin-Ling,Chen, Yong-Jie,Gan, Zong-Jie,Yu, Yu
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p. 1809 - 1814
(2018/07/25)
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- Method for preparing 2,3-dichloro-quinoxaline derivative through one-pot procedure
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The invention belongs to the field of drug synthesis, and specifically relates to a new method for preparing 2,3-dichloro-quinoxaline derivative through one-pot procedure. According to the method, cheap o-phenylenediamine and oxalic acid are adopted as raw materials, and the cheap and easily available and environmentally friendly silica gel or methanesulfonic acid is adopted as a catalyst while steps of intermediate separation and purification are omitted; the method has the advantages of easiness in operation, low cost, mild reaction conditions and environmental friendliness and promotes industrial mass production.
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Paragraph 0020; 0028; 0029; 0030
(2018/07/30)
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- A new small molecule inhibitor of soluble guanylate cyclase
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Soluble guanylate cyclase (sGC) is a haem containing enzyme that regulates cardiovascular homeostasis and multiple mechanisms in the central and peripheral nervous system. Commonly used inhibitors of sGC activity act through oxidation of the haem moiety, however they also bind haemoglobin and this limits their bioavailability for in vivo studies. We have discovered a new class of small molecule inhibitors of sGC and have characterised a compound designated D12 (compound 10) which binds to the catalytic domain of the enzyme with a KD of 11 μM in a SPR assay.
- Mota, Filipa,Gane, Paul,Hampden-Smith, Kathryn,Allerston, Charles K.,Garthwaite, John,Selwood, David L.
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p. 5303 - 5310
(2015/11/11)
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- HETEROCYCLIC INHIBITORS OF HISTAMINE RECEPTORS FOR THE TREATMENT OF DISEASE
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The present invention relates to compounds and methods which may be useful as inhibitors of H1R and/or H4R for the treatment or prevention of inflammatory, autoimmune, allergic, and ocular diseases.
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Page/Page column 66-67
(2011/10/05)
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- HETEROCYCLIC INHIBITORS OF HISTAMINE RECEPTORS FOR THE TREATMENT OF DISEASE
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The present invention relates to compounds and methods which may be useful as inhibitors of H1R and/or H4R for the treatment or prevention of inflammatory, autoimmune, allergic, and ocular diseases.
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Page/Page column 17-18
(2010/06/11)
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- Synthesis of 2,3-dichloroquinoxalines via vilsmeier reagent chlorination
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A convenient and high-yielding synthesis of 2,3-dichloroquinoxalines from the corresponding 2,3- dihydroxyquinoxalines has been developed. Treatment of a slurry of the 2,3-dihydroxyquinoxaline 1a-j with N,N-dimethylformamide in the presence of excess thionylchloride in 1,2-dichloroethane results in the rapid and high-yielding formation of the 2,3-dichloroquinoxaline derivatives 2a-j. Simplified workup and purification procedures for these compounds are also described.
- Romer, Duane R.
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experimental part
p. 317 - 319
(2009/07/19)
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- Fragment based design of new H4 receptor-ligands with anti-inflammatory properties in vivo
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Using a previously reported flexible alignment model we have designed, synthesized, and evaluated a series of compounds at the human histamine H 4 receptor (H4R) from which 2-(4-methyl-piperazin-l-yl)- quinoxaline (3) was identified as a new lead structure for H4R ligands. Exploration of the structure-activity relationship (SAR) of this scaffold led to the identification of 6,7-dichloro 3-(4-methylpiperazin-l-yl) quinoxalin-2(1H)-one (VUF 10214, 57) and 2-benzyl-3-(4-methyl-piperazin-l-yl) quinoxaline (VUF 10148, 20) as potent H4R ligands with nanomolar affinities. In vivo studies in the rat reveal that compound 57 has significant anti-inflammatory properties in the carrageenan-induced paw-edema model.
- Smits, Rogier A.,Lim, Herman D.,Hanzer, Agnes,Zuiderveld, Obbe P.,Guaita, Elena,Adami, Maristella,Coruzzi, Gabriella,Leurs, Rob,De Esch, Iwan J. P.
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p. 2457 - 2467
(2008/12/22)
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- Quinoxaline compounds
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Quinoxaline compounds, compositions, methods of making them, and methods of using them in leukocyte recruitment inhibition, in modulating an H4 receptor, and in treating conditions such as inflammation, H4 receptor-mediated conditions, and related conditions.
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Page/Page column 14
(2008/06/13)
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- Synthesis and Some Reactions of 3-Chloro-2-(cyanomethylene)-1,2-dihydroquinoxalines
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2,3-Dichloroquinoxaline and some of its derivatives have been reacted with malononitrile and ethyl cyanoacetate to yield a variety of 3-chloro-2-(cyanomethylene)-1,2-dihydroquinoxaline derivatives. The reaction of 3-chloro-2-(dicyanomethylene)-1,2-dihydroquinoxaline (2e) with pyridine and its methyl derivatives led to the zwitterionic structures 6a-c. The structures of the newly synthesized compounds were assigned by spectroscopic data and elemental analyses.
- Obefami, Craig A.,Pfleiderer, Wolfgang
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p. 223 - 231
(2007/10/03)
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- Synthesis and Fungicidal Activity of 1,4-Dithiino[2,3-b]quinoxaline-2,3-dicarbonitriles
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A series of eleven 1,4-dithiino[2,3-b]quinoxaline-2,3-dicarbonitriles was prepared by reaction of 2,3-dichloroquinoxalines with disodium (Z)-2,3-dimercapto-2-butenedinitrile in N,N-dimethylformamide. These products were tested for in-vitro fungicidal activity by a Minimum Inhibitory Concentration (MIC) method. Several of these compounds showed broad-spectrum fungicidal activity. The activity exhibited by these compounds was greatly dependent upon the substituents of the quinoxaline ring, with the nitro-substituted derivatives showing the higest levels of antifungal activity. None of the compounds prepared, however, showed fungicidal activity comparable to that of the commercial fungicides screened.
- Romer, Duane R.,Aldrich, Brian L.,Pews, R. Garth,Walter, Richard W.
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p. 263 - 266
(2007/10/03)
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- Permanganate Oxidation of Quinoxaline and Its Derivatives
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The oxidation reaction of a series of quinoxaline derivatives, using KMnO4 in the presence or absence of NaOH, are described.Neutral oxidation of 2-chloro- and 2,3-dichlorodioxalines 2-4 afforded the corresponding chloro- and dichloropyrazinedicarboxilic acids 13 and 14 in good yield.On the other hand, oxidation of quinoxalin-2(1H)-one and 1,4-dihydroquinoxaline-2,3-dione derivatives in alkaline medium gave different products, with the quinoxalin-2(1H)-one (5) forming 1,4-dihydroquinoxaline-2,3-dione (9), while various substituted quinoxalin-2,3-dione derivatives (see 9-11) gave a new type of dimeric products.The structural assignments for the new compounds were based on spectroscopic data.
- Obafemi, Craig A.,Pfleiderer, Wolfgang
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p. 1549 - 1556
(2007/10/02)
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- Synthesis of Pyridoimidazoquinoxalines
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Synthesis of pyridoimidazoquinoxalines by the facile cyclizations of 2,3-dichloroquinoxalines with 2-aminopyridines and of 2-amino-3-chloroquinoxalines with various substituted pyridines is described.
- Tanaka, Kiyoshi,Takahashi, Hideki,Takimoto, Kozo,Sugita, Masahiko,Mitsuhashi, Keiryo
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p. 771 - 777
(2007/10/02)
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- 4-Aminotriazoloquinoxalines. A Novel Class of Potent Adenosine Receptor Antagonists and Potential Rapid-Onset Antidepressants
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A series of 4-aminotriazoloquinoxalines has been prepared.Many compounds from this class reduce immobility in Porsolt's behavioral despair model in rats upon acute administration and may therefore have therapeutic potential as novel and rapid acting antidepressant agents.Optimal activity in this test is associated with hydrogen, CF3, or small alkyl groups in the 1-position, with NH2, NH-acetyl, or amines substituted with small alkyl groups in the 4-position, and with hydrogen or 8-halogen substituents in the aromatic ring.Furthermore, many of these 4-aminoquinoxalines bind avidly, and in some cases very selectively, to adenosine A1 and A2 receptors.A1 affinity of these compounds was measured by their inhibition of tritiated CHA (N6-cyclohexyladenosine) binding in rat cerebral cortex membranes and A2 affinity by their inhibition of tritiated NECA (5'-(N-ethylcarbamoyl)adenosine) binding to rat striatal homogenate in the presence of cold N6-cyclopentyladenosine.Structure-activity relationship (SAR) studies show that best A1 affinity is associated with ethyl, CF3, or C2F5 in the 1-position, NH-iPr or NH-cycloalkyl in the 4-position, and with an 8-chloro substituent.Affinity at the A2 receptor is mostly dependent on the presence of an NH2 group in the 4-position and is enhanced by phenyl, CF3, or ethyl in the 1-position.The most selective A1 ligand by a factor of >3000 is 121 (CP-68,247; 8-chloro-4-(cyclohexylamino)-1-(trifluoromethyl)triazoloquinoxaline) with an IC50 of 28 nM at the A1 receptor.The most potent A2 ligand is 128 (CP-66,713; 4-amino-8-chloro-1-phenyltriazoloquinoxaline) with an IC50 of 21 nM at the A2 receptor and a 13-fold selectivity for this receptor.Representatives from this series appear to act as antagonists at both A1 and A2 receptors since they antagonize the inhibiting action of CHA on norepinephrine-stimulated cAMP formation in fat cells and they decrease cAMP accumulation induced by adenosine in limbic forebrain slices.Thus certain members of this 4-aminotriazoloquinoxaline series are among the most potent and A1 or A2 selective non-xanthine adenosine antagonists known.
- Sarges, Reinhard,Howard, Harry R.,Browne, Ronald G.,Lebel, Lorraine A.,Seymour, Patricia A.,Koe, B. Kenneth
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p. 2240 - 2254
(2007/10/02)
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- Synthesis and Biological Activities of Some 1,5-Dihydroditriazolo-quinoxaline-1,6-diones
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Some new 1,5-dihydroditriazoloquinoxaline-1,6-diones (IV) have been prepared and tested for their antiallergic, antimicrobial, antiprotozoal and anthelmintic activities.Compounds IVe,d,f are found to posess promising egg albumin-induced rat passive cutaneous anaphylaxis (PCA) activity by showing more than 90percent inhibition at 50 mg/kg dose
- Sastry, C. V. Reddy,Jogibhukta, M.,Krishnan, V. S. H.,Rao, P. Shanthan,Vemana, K.,et al.
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p. 1110 - 1112
(2007/10/02)
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- Method of using [1,2,4]triazolo[4,3-a]quinoxaline-4-amine derivatives as antidepressant and antifatigue agents
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A series of novel [1,2,4]triazolo[4,3-a]quinoxaline-4-amine derivatives wherein the amine group is optionally substituted with lower alkyl, phenylalkyl having up to three carbon atoms in the alkyl moiety or alkanoyl having from two to five carbon atoms, or the amine group alternatively completes a piperazino ring, the quinoxaline ring is optionally substituted with fluorine, chlorine, bromine or methoxy, and the triazolo ring is optionally substituted with lower alkyl, lower perfluoroalkyl or phenyl are disclosed. These novel compounds are useful for treatment of symptoms associated with depression. Also disclosed are pharmaceutical compositions containing the novel compounds of this invention and a method of using the compounds in the treatment of depression and fatigue.
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- Method of using [1,2,4]triazolo[4,3-a]quinoxaline-4-amine derivatives as antidepressant and antifatigue agents
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A series of novel [1,2,4]triazolo[4,3-a]quinoxaline-4-amine derivatives wherein the amine group is optionally substituted with lower alkyl, phenylalkyl having up to three carbon atoms in the alkyl moiety or alkanoyl having from two to five carbon atoms, or the amine group alternatively completes a piperazino ring, the quinoxaline ring is optionally substituted with fluorine, chlorine, bromine or methoxy, and the triazolo ring is optionally substituted with lower alkyl, lower perfluoroalkyl or phenyl are disclosed. These novel compounds are useful for treatment of symptoms associated with depression. Also disclosed are pharmaceutical compositions containing the novel compounds of this invention and a method of using the compounds in the treatment of depression and fatigue.
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- A Versatile New Synthesis of Quinolines and Related Fused Pyridines. Part 5. The Synthesis of 2-Chloroquinoline-3-carbaldehydes
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Acetanilides are converted into 2-chloroquinoline-3-carbaldehydes in good yield by the action of Vilsmeier's reagent in phosphoryl chloride solution.The reaction is shown to involve successive conversion of the acetanilide into an imidoyl chloride and then an N-(α-chlorovinyl)aniline.The latter enamine is diformylated at its β-position and subsequently cyclised to the chloroquinolinecarbaldehyde.The diformylated intermediates may be isolated in several cases and separately cyclised with polyphosphoric acid.
- Meth-Cohn, Otto,Narine, Bramha,Tarnowski, Brian
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p. 1520 - 1530
(2007/10/02)
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