Synthesis of 2,3-dihydro-4(1H)-quinoline derivatives

N-Carboxyethyl-N-(3-R-phenyl)-ß-alanines were synthesized by the reaction of m-substituted anilines with acrylic acid; they were cyclized to the corresponding 2,3-dihydro-4(1H)-quinoline derivatives.Translated from Khimiva Geterotsiklicheskikh Soedinenii. No. 4, pp. 523–526, April, 1996.     

New 4(5H)-oxazolonium perchlorate derivatives

The condensation of 2,3-dimethyl-4(5H)-oxazolonium salts with ethyl orthoformate and amides of 5-substituted 2-furancarboxylic acids gives the corresponding products derived by modification of the methyl group at C₍₂₎, 2-formylmethylene-4-oxazolidinone and 2-furoylaminoethenyl-4(5H)-oxazolanium perchlorates.Kuban State Technological University, 350072, Krasnodar. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 236–237, February, 1995. Original article submitted September 30, 1994.     

Synthesis of new 4(3H)-quinazolinone derivatives using 5(4H)-oxazolones

New derivatives of 5(4H)-quinazolinone containing 2-imidazolin-5-one rings have been prepared from 5(4H)-oxazolone derivatives.     

5-甲基-2，3-二苯基-1，5-苯并硫氮杂卓-4(5H)-酮的合成

以2-甲硫基苯胺为原料,通过酰化、碘环化以及Suzuki交叉偶联反应,合成了5-甲基-2,3-二苯基-1,5-苯并硫氮杂卓-4(5H)-酮。 分别考察了催化剂对酰化反应、溶剂对碘环化反应的影响,以及催化剂、配体、碱和温度等因素对Suzuki交叉偶联反应的影响,在最佳的反应条件下,反应总收率为68.5%,中间产物和目标产物的结构经IR、NMR和MS等测试技术得以确证。     

Synthesis and reactivity of thieno[2,3-b]quinoline derivatives (Part II)

As a continuation of our previous review entitled “Vilsmeier-Haack cyclisation as a facile synthetic route to thieno[2,3-b]quinolines (Part I).” This review describes the methods of preparation and the chemical reactivity of thieno[2,3-b]quinolines, which might show interesting biological activities.     

4-Anilinopyrimido[4',5':4,5]selenolo(2,3-b)quinoline and 4-piperazino pyrimido[4',5':4,5]selenolo(2,3-b)quinoline: new DNA intercalating chromophores with antiproliferative activity

We have used circular dichroism, hydrodynamic methods, absorbance, and fluorescence titration to study the interaction of 4-anilinopyrimido[4',5':4,5] selenolo (2,3-b)quinoline (APSQ) and 4-piperazinopyrimido[4',5':4,5] selenolo(2,3-b)quinoline (PPSQ) with DNA. The association constants of APSQ and PPSQ were of the order of 10(4)M(-1). The fluorescence properties at ionic strength 0.01M are best fit by the neighbor exclusion model, with K=0.58-9.2 x 10(4)M(-1) and an exclusion parameter of 0.9-6.4 bp. Binding to the GC-rich DNA of Micrococcus lysodeikticus was stronger than the binding to calf thymus DNA, suggest that drug binds preferentially to G+C pairs at low r. CD spectra indicate that stacking of these compounds with DNA induces a strong helicity in the usually disordered structure of this double strand. Viscosity experiments show with sonicated calf thymus DNA with PPSQ an twice increase in slope (m) as that with APSQ. PPSQ increases the T(m) for calf thymus DNA melting by approximately 10 degrees C as binding approaches saturation, with biphasic melting. The cytotoxicities of these compounds on leukemia HL-60, K-562, B16F10 melanoma and Colo-205 are quite similar and inhibition (IC(50)) was in the range of 0.39-9.80 microM. The anticancer efficacy against B16F10 melanoma has provided evidence of major anticancer activity for PPSQ. Single or multiple intraperitonial (i.p.) doses of drug proved high level activity against the subcutaneous (s.c.) grafted B16 melanoma, significantly increase in life span (ILS 139% and 170%). The aim of this study was to analyze the physiochemical properties of these compounds in an attempt to understand its superior biological activity.     

The transformations of 4-heteroarylaminomethylene-5(4H)-oxazolones into dehydropeptide derivatives

2-Phenyl-4-heteroarylaminomethylene-5(4H)-oxazolones 3 , which were prepared from the corresponding N,N-dimethyl-N'-heteroarylformamidines 1 and hippuric acid 2 in acetic anhydride, react with amino acids giving dehydropeptide derivatives 4, 5 , and 6 as products. Dehydration of N-protected peptides 7–10 , containing glycine at the C-terminal, followed by the reaction with formamidines 1 gave 2-substituted-4-heteroarylaminomethylene-5(4H)-oxazolones 11–14 .     

Electron impact-induced fragmentation of 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones

The electron impact-induced fragmentations of 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones and some related compounds were investigated. On the basis of low- and high-resolution measurements, metastable ion studies by means of mass-analysed ion kinetic energy spectroscopy and collision-induced dissociation experiments, the main fragmentation pathways were established. The effect of methyl and phenyl substituents at the C(2) and C(3) positions of the heterocyclic ring on the fragmentations was also studied. The (1,3) ring splitting was investigated in some detail, using semi-empirical molecular orbital calculations.     

Solution-phase parallel synthesis of 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones

Practical and efficient parallel methods have been developed for the synthesis of 7,8-disubstituted 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones and 3,7,8-trisubstituted 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones. This benzothiazepin-4(5H)-one skeleton possesses three or four diversity points. Furthermore, three novel tricycles integrating a benzothiazepin-4(5H)-one scaffold with other privileged structures, such as benzimidazole, benzimidazolone, and thio-benzimidazole, were also developed. The synthetic strategy provides an efficient way to access the benzothiazepinone core, starting from commercially available 1,5-difluoro-2,4-dinitrobenzene (DFDNB), and also allows further derivation of the strategically anchored functionalities.     

Indole derivatives. 135. 5-[2-(4-Methoxyphenyl)ethenyl]indolines and indoles

5-[2-(4-Methoxyphenyl)ethenyl]indolines were obtained from 5-formyl-1-methyl- or 5-forrayl-1-benzylindolines by the Witting reaction with 4-methoxybenzylidenetriphenylphosphorane. Their dehydrogenation led to the formation of the corresponding compounds of the indole series. The corresponding hydroxy compounds were obtained by demethylation of the methoxyindole with boron tribromide and were converted into the acetoxy derivatives of indoline and indole.For communication 134, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 911–914, July, 1989.     

Synthesis and mechanism of formation of 5-benzylidene-2-thioxo-2,3-dihydro-(1H,5H)-pyrimidine-4,6-diones difluoromethoxy derivatives

Reactions of 5-benzylidene-2-thioxo-2,3-dihydro-(1H,5H)-pyrimidine-4,6-diones with a singlet difluorocarbene afford difluoromethoxy derivatives in 20–34% yield. The quantum-chemical analysis of the reaction mechanism showed that N,N-dimethylformamide is involved into the formation of difluoromethoxy derivatives.     

Novel syntheses of 3-cyano-3,4-dihydroquinolin-2(1H)-one and derivatives of 2,3-dicarbomethoxy-2-hydroxycyclopenta[b]quinoline

A facile solid phase conversion of 2-chloro-3-cyano-4-substituted-1,4-dihydroquinolines to 3-cyano-4-substituted-3,4-dihydroquinolin-2(1H)-ones in almost quantitative yields and a novel synthesis of 2,3-dicarbomethoxy-2-hydroxycyclopenta[b]quinoline are described.     

Indole derivatives. 124. 5-(2-phenylethenyl)indolines and 5-(2-phenylethenyl)indoles

5-(2-Phenylethenyl)indolines, the dehydrogenation of which leads to the formation of the corresponding compounds of the indole series, were obtained from 5-formyl-1-methyl(or benzyl)indolines via the Grignard reaction with benzyl-magnesium chloride and subsequent dehydration. The hormonal activity of the synthesized compounds was studied.See [1] for communication 123.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No, 4, pp. 466–469, April, 1984.     

4-bromo-5-methyl-(2H)-1,2,6-thiadiazin-3(6H)one 1,1-dioxides

The title compounds, bearing an alkyl and/or bromine substituent on nitrogen, were synthesized. Unlike 5-bromo-6-methyluracil, 4-bromo-5-methyl-(2H)-1,2,6-thiadiazin-3-(6H)one 1,1-dioxides have the ability to act as a bromonium ion source.     

Acid-catalyzed rearrangement of 2-phenyl-2,3-dihydro-1,4-benzoxazepin-5(4H)ones

2-Phenyl-2,3-dihydro-1,4-benzoxazepin-5(4H)ones (I) were converted into 2-(o-hydroxyaryl)-5-plienyl-2-oxazolines (II) and 3,4-diliydro-4-plienyl-8-hydroxyisoearbostyrils (III) by concentrated sulfuric acid. The ratio of II and III is dependent upon substituents present in the aromatic ring of the parent benzoxazepinones.