The Synthesis and Antimicrobial Screening of Some Novel AZA-Imidoxy Compounds as Potential Chemotherapeutic Agents

Some novel azaimidoxy compounds viz. 2-{[(4-chlorophenyl)diazenyl]oxy}-1H-isoindole-1,3-(2H)-dione (Va), and 1-{[1-naphthyldiazenyl]oxy}pyrrolidine-2,5-dione (IVc), etc. have been synthesized by a simple diazotization reaction followed by a coupling with 2-hydroxy-1H-isoindole-1,3(2H)-dione (III)/1-hydroxypyrrolidine-2,5-dione (II) of corresponding aromatic primary amine derivatives at a suitable pH. A similar reaction with a [1,3]thiazolo[4,5-b]pyridin-2-amine (VIII) lead us to some interesting results variable with a pH. The structure of all synthesized compounds has been established by IR, ¹H NMR, and mass studies. These compounds have been screened for antimicrobial activities in order to evaluate the possibility of the derivatives to be used as potential chemotherapeutic agents.     

Synthesis and antitumor evaluation of novel tetrahydrobenzo[4′,5′]thieno[3′,2′:5,6]pyrimido[1,2-b]isoquinoline derivatives

In the present study, a novel 8,9,10,11-tetrahydro-7H,14H-benzo[4′,5′] thieno[2′,3′:4,5]-1,3-oxazino[3,2-b]isoquinoline-7,14-dione 5 was prepared by condensation of 2-amino-3-carbethoxy-4,5,6,7-tetrahydrobenzothiophene with homophthalic anhydride under microwave irradiation, followed by alkaline hydrolysis and cyclization using acetyl chloride. Compound 5 was further allowed to react with different nitrogen nucleophiles to get new tetrahydrobenzothienopyrimido isoquinolinone derivatives. The structures of the prepared compounds were elucidated by IR, ¹H-NMR, ¹³C-NMR, and mass spectroscopy. The newly prepared compounds were tested in vitro against a panel of two human tumor cell lines, namely, hepatocellular carcinoma (liver) HepG2, and mammary gland breast MCF-7. Almost all the tested compounds showed satisfactory activity.     

Synthesis and cytotoxic activity against human tumor cells of heterocyclic systems derived from 2-thioxo-1,2-dihydro-4H-3,1-benzothazin-4-one

The title compound was prepared and converted to 2-hydrazinyl-1,2-dihydro-4H-benzo[d][1,3]thiazin-4-one which was utilized to synthesize fused heterocyclic systems, namely benzotriazolothiazinone derivatives, as well as, nonfused heterocyclic systems such as pyrazolyl-benzothiazinones, benzothiazinylpyridazine and imidazolylbenzothiazinone derivatives via reaction with formamide, acetic acid, ethyl cyanoacetate, maleic anhydride and benzaldehyde followed by treatment with glycine, respectively. All compounds have been structurally characterized by means of IR, MS, and ¹H-NMR spectra. The synthesized compounds were evaluated in vitro for their antiproliferative activity against HePG-2 and MCF-7 cell lines. 2H-Benzo[d][1,3]thiazine-2,4(1H)-dithione and 2-thioxo-1,2-dihydro-4H-benzo[d][1,3]thiazin-4-one were the most potent against the two cancer cells compared to that of the reference compound doxorubicin. Most of the synthesized compounds also exhibited good cytotoxic activity.     

新型多重氮杂杯[4]芳烃衍生物的合成

对叔丁基杯[4]芳烃-1,3-二醛基衍生物1与水杨酰肼、烟酰肼、异烟酰肼反应, 合成了具有开链结构新型杯[4]多重氮杂衍生物2a～2c, 产率分别为88%, 85%和90%. 化合物1与乙二酰肼、丙二酰肼、己二酰肼反应, 得到具有桥联结构的新型杯[4]多重氮杂衍生物3a～3c, 产率分别为86%, 89%和90%. 新化合物的结构经元素分析、质谱、核磁共振谱等表征证实, 杯[4]芳烃单元均为1,3-取代且采取锥式构象.     

Functional polymers LII Synthesis and polycondensation of 2(2,4-Dihydroxyphenyl)2H-1,3-bis[4-carboxy (or 4-carbomethoxy)2H-benzotriazole]

Carboxy- and carbomethoxy derivatives of resorcinols with two benzotriazole substituents have been synthesized. 2(2,4-Dihydroxyphenyl)2H-1,3-bis-(4-carboxybenzotriazole) [2,4-bis(2H-4-carboxybenzotriazole-2-yl)-1,3-dihydroxybenzene] (DCBDH) was prepared by azo coupling of 4-carboxy-2-nitrobenzene diazonium chloride with resorcinol followed by reductive cyclization. 2(2,4-Dihydroxyphenyl)2H-1,3-bis(4-carbomethoxy-benzotriazole) [2,4-bis-(2H-4-carbomethoxy-benzotriazole-2-yl)-1,3-dihydroxybenzene] (DCMBDH) was obtained by esterification of the free dicarboxylic acid with methanol. The compounds were characterized by their elemental analyses and melting points, and by their IR, UV,¹H NMR, and¹³C NMR spectra.Copolycondensations were carried out to incorporateDCBDH orDCMBDH into polyamides or polyesters. The condensation copolymers were briefly characterized.Functional Polymers LI:M. D. Purgett,W. J. MacKnight, andO. Vogl, Polym. Eng. and Sci.27(19), 1461 (1987)     

Synthesis,ABTS-Radical Scavenging Activity,and Antiproliferative and Molecular Docking Studies of Novel Pyrrolo[1,2-a]quinoline Derivatives

A new 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)-radical scavenging and antiproliferative agents of pyrrolo[1,2-a]quinoline derivatives have been synthesized. An efficient method for the synthesis of 14 novel diversified pyrrolo[1,2-a]quinoline derivatives has been described using 4-(1,3-dioxolan-2-yl)quinoline and different phenacyl bromides in acetone and followed by reacting with different acetylenes in dimethylformamide/K₂CO₃. The structure of the newly synthesized compounds was determined by infrared, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. The in vitro antioxidant activity revealed that among all the tested compounds 5n exhibited maximum scavenging activity with ABTS. Compound 5b has showed good antiproliferative activity as an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase.     

Regiocontrolled Incorporation and Annulation of Glucose into Spirothiazole and Spirothiazoloxazole Derivatives

ABSTRACT

Cyclic ketones 1a-f reacted with mercaptoacetic acid in benzene and/or toluene in the presence of p-toluenesulfonic acid afforded the corresponding spiro-1,3-oxathialanone derivatives (2a-f). Compounds 2a-f reacted with glucosamine hydrochloride in a mixture of pyridine and ethanol to yield 3-(2′-glucosyl)-2-spiro[1′-cycloalkyl]thiazolidin-4-one derivatives 4a-f. Reaction of 4a-f with fused sodium acetate in a mixture of acetic anhydride and acetic acid gave annulated spirothiazoloxazologlucose derivatives 6a-f. All the synthesized spiro derivatives were identified by conventional methods (IR, ¹H NMR spectroscopy and elemental analyses).     

Novel Triphenylamine Appended 1,3-Alternate-Calix[4]arenes: Synthesis and Characterization

In the present study, two novel calix[4]arene receptors containing triphenylamine units in 1,3-alternate conformation have been synthesized and characterized in detail. First, the 25,27-dipropoxy-26,28-bis[(3-aminopropyl)oxy]-calix[4]arene 4 and 25,26,27,28-tetra[(3-aminopropyl)oxy]-calix[4]arene 7 were prepared by using convenient reagents. Then, these amino derivatives of calix[4]arene were converted to Schiff base derivatives appended to triphenylamine of calix[4]arene (5 and 8) using 4-formyltriphenylamine via condensation. The 1,3-alternate conformation of the synthesized calix[4]arenes was determined by ¹H and ¹³C NMR analyses. Also, their structures have been characterized by using ¹H and ¹³C NMR, infrared, and elemental analyses.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

杯[4]芳烃二肟酸-Cu(Ⅰ)配合物的设计与自组装合成

Cu是许多酶中的必须元素[1],Cu与有机配体形成的配合物不仅具有氧化、还原、催化、超分子化合物结构控制等重要作用,而且具有抗菌、抗癌、抗病毒等生物活性.     

Synthesis,spectral characterization,and evaluation of antimicrobial activity of O,O′-alkanediyl S-(N-phthalimidomethyl) dithiophosphates and zinc bis(O,O′-alkanediyl) dithiophosphates

The synthesis of novel dithiophosphate derivatives has been achieved. Two O,O′-alkanediyl S-(N-phthalimidomethyl) dithiophosphates and two Zinc bis(O,O′-alkanediyl) dithiophosphates are synthesized by an easy and facile chemical synthetic route. Zinc bis[O,O′-(2-methylpentane-2,4-diyl) dithiophosphate] L¹, Zinc bis[O,O′-(2-ethylhexane-1,3-diyl) dithiophosphate] L², O,O′-(2-methylpentane-2,4-diyl) S-(N-phthalimidomethyl) dithiophosphate L³ and O,O′-(2-ethylhexane-1,3-diyl) S-(N-phthalimidomethyl) dithiophosphate L⁴ are synthesized from the respective ammonium salts. Compounds L¹, L², L³, and L⁴ are characterized by (CHN) elemental analysis, ESI mass, FT-IR, ¹H, ¹³C, and ³¹P NMR techniques. The crystal structure of ammonium O,O′-(2-methylpentane-2,4-diyl) dithiophosphate is discussed. L¹, L², L³, and L⁴ were evaluated for antimicrobial activity. It was found that the phthalimide derivatives L³ and L⁴ showed much better antifungal potential against some species of fungus. The Zinc dithiophosphates L¹ and L² showed good antibacterial activity against Bacillus cereus and Escherichia coli.     

Charge-Transfer Salts of Ferrocene Derivatives with Bis(maleonitriledithiolato)metallate(III) Complexes ([M(mnt)2]−, M=Ni,Pt): A Ground-State High-Spin [(Ni(mnt)2)2]2− Dimer

New hexamethylated ferrocene derivatives containing thioether moieties (1,1′-bis[(tert-butyl)thio]-2,2′,3,3′,4,4′-hexamethylferrocene ( 3a , b )) or fused S-heteropolycyclic substituents (rac-1-[(1,3-benzodithiol- 2-yliden)methyl]-2,2′,3,3′,4,4′-hexamethylferrocene ( 5 ) and rac-1-[1,2-bis(1,3-benzodithiol-2-yliden)ethyl]-2,2′,3,3′,4,4′-hexamethylferrocene ( 14 )), as well as a series of ferrocene-substituted vinylogous tetrathiafulvalenes (1,1′-bis[1,2-bis(1,3-benzodithiol-2-yliden)ethyl]ferrocene ( 6a ), 1,1′-bis[1-(1,3-benzodithiol-2-yliden)-2-(5,6-dihydro-1,3-dithiolo[4,5-b] [1,4]dithiin-2-yliden)ethyl]ferrocene ( 6b ), [1,2-bis(1,3-benzodithiol-2-yliden)ethyl]ferrocene ( 21a ), [1-(1,3-benzodithiol-2-yliden)-2-(5,6-dihydro-1,3-dithiolo[4,5-b] [1,4]dithiin-2-yliden)ethyl]ferrocene ( 21b ), [1,2-bis(5,6-dihydro-1,3-dithiolo[4,5-b] [1,4]dithiin-2-yliden)ethyl]ferrocene ( 21c ), [1-(5,6-dihydro-1,3-dithiolo[4,5-b] [1,4]dithiin-2-yliden)-2-(1,3-benzodithiol-2-yliden)ethyl]ferrocene ( 21d )) were prepared and fully characterized. Their redox properties show that some of them are easily oxidized and undergo transformation to paramagnetic salts containing bis(maleonitriledithiolato)-metallate(III) anions [M(mnt)₂]⁻ (M=Ni, Pt; bis[2,3-dimercapto-κS)but-2-enedinitrilato(2⁻)]nickelate (1⁻) or -platinate (1⁻). The derivatives [ 3a ] [Ni(mnt)₂] ( 26 ), [ 3a ] [Pt(mnt)₂] ( 27 ), [Fe{(η⁵-C₅Me₄S)₂S}] [Ni(Mnt)₂] ( 28 ), [Fe{(η⁵-C₅Me₄S)₂S}] [Pt(mnt)₂] ( 29 ), [ 5 ] [Ni(mnt)₂]⋅ClCH₂CH₂Cl ( 30 ), [ 6a ] [Ni(mnt)₂] ( 31 ), [ 6a ] [Ni(mnt)₂]⋅ClCH₂CH₂Cl ( 31a ), [ 6a ] [Pt(mnt)₂] [ 32 ), and [ 6b ] [Ni(mnt)₂] ( 33 ) were prepared and fully characterized, including by SQUID (superconducting quantum interference device) susceptibility measurements. X-Ray crystal-structural studies of the neutral ferrocene derivatives 6a , b , 21c , d , and 1,1′-bis[1-(1,3-benzodithiol-2-yliden)-2-oxoethyl]ferrocene ( 23 ), as well as of the charge-transfer salts 26 – 28 , 30 , and 31a , are reported. The salts 28 and 30 display both a D⁺A⁻A⁻D⁺ structural motif, however, with a different relative arrangement of the [{Ni(mnt)₂}₂]²⁻ dimers, thus giving rise to different but strong antiferromagnetic couplings. Salt 26 exhibits isolated ferromagnetically coupled [{Ni(mnt)₂}₂]²⁻ dimers. Salt 27 displays a D⁺A⁻D⁺A⁻ structural motif in all three space dimensions, and a week ferromagnetic ordering at low temperature. Salt 31a , on the contrary, shows segregated stacks of cations and anions. The cations are connected with each other in two dimensions, and the anions are separated by a 1,2-dichloroethane molecule.     

Synthesis and Properties of New Thiacalixarene Derivatives with Palladium Ion

Three new thiacalix[4]arene derivatives, 5,11,17,23-tetra-tert-butyl-25,27-di(2-hydroxyethoxy)-26,28-dihydroxythiacalix-{}[4]arene (2), 5,11,17,23-tetra-tert-25, 26,27,28-tetrakis[(methylcarboxyl)methoxy]thiacalix[4]arene (3),5,11,17,23-tetra-tert-butyl-25,26,27,28-tetrakis(2-hydroxy-1-propanoxy)thiacalix[4]arene (4), were synthesized for the first time. The coordination properties of thiacalix[4]arene(1) and its derivatives (2 and 4) were investigated by detecting the interactions betweenthese compounds and two palladium complexes, cis-[Pd(en)(H₂O)₂]²⁺ and cis-[Pd(dtco-3-OH)(H₂O)₂]²⁺, by means of electrospray ionization mass spectrometry (ESI-MS) technique.     

Pyrido[1,2‐a]pyrimidin‐4‐ones: Ligand‐based Design,Synthesis, and Evaluation as an Anti‐inflammatory Agent

In the present study, a series of novel pyrido[1,2‐a]pyrimidin‐4‐one derivatives ( 1 – 45 ) were synthesized, characterized, and evaluated for their anti‐inflammatory activity. The structures of all newly synthesized compounds were confirmed by ¹H NMR, ¹³C NMR, mass spectroscopy, and C, H, and N analyses. Preliminary these newly synthesized compounds were evaluated for their in vitro cyclooxygenase (COX)‐2/COX‐1 inhibitory activity. The celecoxib, a COX‐2 inhibitor, was used as a reference standard drug. In this inhibitory study, compounds 42 , 43 , 44 , and 45 were found to have significant in vitro inhibitory profile as compared with the reference drug. These compounds were then subjected to their in vivo anti‐inflammatory assay by using carrageenan‐induced rat paw edema method in next level of screening. Later, these same compounds were tested for their ulcerogenic property. Based on these activity data, the compound 43 (in vitro COX‐2 activity—IC₅₀ = 0.4 μM, SI = 400, in vivo anti‐inflammatory activity—72% inhibition after 3 h, and 0.38%—Ulcer index) was emerged as most promising anti‐inflammatory agent with very low ulcerogenic action.     

New substituted 2-aminomethyl-2-oxo-2λ5-perhydro-[1,3,2]oxazaphospholo [3,4-a]pyridine: Design,synthesis and antimicrobial activity

The synthesis of a new series of P-heterocyclic compounds, substituted 2-aminomethyl-2-oxo-2λ⁵-perhydro-[1,3,2]oxazaphospholo[3,4-a]pyridine derivatives 8(a-j), was accomplished. A key intermediate, 2-(chloromethyl)-2-oxo-2λ⁵-perhydro-[1,3,2]oxazaphospholo[3,4-a]pyridine (6) was primarily synthesized by the condensation of (±)-2-piperidinemethanol (4) and chloromethylphosphonic dichloride (5); subsequently, it was treated with various heterocyclic amines/benzylamines/aminoacid esters, 7(a-j) to obtain the desired products. The structures of the newly synthesized compounds were elucidated by ¹H, ¹³C, and ³¹P NMR spectroscopy, mass spectra and elemental analyses. The biological potency of title products was investigated by screening in vitro antimicrobial activity. The bio-screening data revealed that most of the synthesized derivatives showed potent growth of inhibition against fungi while compared with bacteria. Particularly, compounds 8c and 8i against bacterial strains, and 8a and 8f against fungi exhibited promising activity.     

Synthesis of quinazolino-1,3-benzothiazine derivatives

The ring-closure reactions of N-(3,4-dimethoxyphenylthiomethyl)-2-nitrobenzamide derivatives 5a,b with phosphoryl chloride gave 4-(2-nitrophenyl)-2H1,3-benzothiazine derivatives 7a,b , which on reduction yielded 4-(2′-aminophenyl)-3,4-dihydro-2H-1,3-benzothiazines 8a,b. Reaction of these compounds with phosgene led to a new heterocyclic ring system, 6H,8H-quinazolino[3,4-c][1,3]benzothiazine derivatives 9a,b. The structures of the title compounds were proved via their ir and nmr (¹H, ¹³C) spectra.     

Synthesis,reactions, and antimicrobial evaluations of new benzo[e][1,3]thiazine derivatives

4H-Spiro[benzo[d][1,3]oxathiine-2,1′-cyclohexan]-4-one undergoes aminolysis with certain aromatic amines to give the respective 4-benzenesulfonamide, Ethyl benzoate, and 4-acetylphenyl of 4-oxospirobenzo[e][1,3]thiazine derivatives. The Schiff bases prepared by reacting Ethyl benzoate derivative 2a with aldehydes, undergoes cyclocondensation with thioglycolic acid yielding p-methoxyphenyl and 2-(thiophen-2-yl) thiazolidinone derivatives. Treatment of the benzoate derivative with hydrazine hydrate afforded the corresponding benzohydrazide derivative which upon reaction with phenyl isocyanate and phenyl isothiocyanate afforded the urea and thiourea derivatives. New pyrimidine, pyridone, and imino pyridine derivatives of 4-oxospirobenzo[e][1,3]thiazine were also successfully prepared by reacting 2b or 2c with the appropriate organic reagents. Structural elucidations for the new products were based upon compatible microanalytical and spectroscopic measurements. Besides, their biological screening indicated that they possess potent antimicrobial activity in comparison with reference drugs.     

One-Pot,Multicomponent Condensation Reaction in Neutral Conditions: Synthesis,Characterization, and Biological Studies of Fused Thiazolo[2,3-b]quinazolinone Derivatives

A new series of 12-(2-chloro-6-quinoline-3-yl)-3,3,8-substituted-2,3,4,12-tetrahydro-benzo[4,5]thiazolo[2,3-b]quinazolin-1-ones 4 was synthesized in one pot by condensing various 2-chloro-3-formylquinolines 1, 2-amino-6-substituted-benzothiazoles 2, and 1,3-cyclohexanedione 3 in ethanol. All the compounds were characterized by IR, ¹H NMR, ¹³C NMR spectra and elemental analysis. All the synthesized compounds were screened for their antibacterial activity against Grampositive bacterial species Bacillus cereus and Bacillus substilus, Gram-negative bacterial species Escherichia coli, and their fungicidal activity against Aspergillus niger, Fuserium oxisporum, and Rhizopus species.     

Complexes of Co(II), Ni(II), Cu(II), and Pd(II) with Sulfametrole-Cyclodiphosph(V)azane Derivatives

Novel [1,3-di-[N ₁ -4-methoxy-1,2,5-thiadiazole-3-yl-sulfanilamide(sulfametrole)]-2″4-bis-[1,3-dithiole-2-thione-4,5-dithiolate]-2′,4′-dichl-orocyclodiphosph(V)azane] (III) , was prepared and their coordinating behavior towards the metal ions Co(II), Ni(II), Cu(II), and Pd(II) was studied. The structures of the isolated products are proposed based on elemental analyses, IR, UV, ¹ H, and ³¹ P NMR, ESR, magnetic susceptibility, molar ratio, conductometric titration and electrical conductivity measurements. The prepared complexes showed high to moderate bactericidal activity compared with the ligand.     

Synthesis of Some New 3-Oxo-2-[(Z)-1-phenylmethylidene]-5H-[1,3]thiazolo[3,2-a]-and N-Acetylated Pyrimidines

3-Oxo-2-[(Z)-1-phenylmethylidene]-5H-[1,3]thiazolo[3,2-a] pyrimidine derivatives 2a–f were synthesized by the reaction of an appropriate 3,4-dihydro-2(H)-pyrimidone 1 , chloroacetic acid, sodium acetate and benzaldehyde. Reaction of 1 with acetic anhydride under heating afforded only 3-N-acetylated 3,4-dihydro-2(H)-pyrimidines 3a–f . The yields of the products after recrystallization from ethanol were of the order of 60–92 %. IR, ¹ H NMR spectroscopy, and elemental analysis were used for the identification of these compounds.     

Synthesis and Pharmacological Evaluation of Some Novel Imidazo[2,1-b][1,3,4]thiadiazole Derivatives

Synthesis of bis‐1,3‐{6′‐arylimidazo[2,1‐b][1,3,4]thiadiazol‐2‐yl}‐1,2,2‐trimethylcyclopentane ( 3 ), bis‐1,3‐{thiadiazolo[2′,3′:2,1]imidazo[4,5‐b]quinoxalinyl}‐1,2,2‐trimethylcyclopentane ( 5 ) has been achieved by the reaction of bis‐(5′‐amino‐1′,3′,4′‐thiadiazolyl)‐1,2,2‐trimethylcyclopentane with α‐haloketones, 2,3‐dichloroquinoxaline respectively. Bromination of compound 3 furnished bis‐1,3‐{5′‐bromo‐6′‐arylimidazo[2,1‐b][1,3,4]thiadiazol‐2‐yl}‐1,2,2‐trimethylcyclopentane ( 4 ). The structural assignment of these compounds was supported by IR, ¹H NMR and elemental analysis data. The antimicrobial, anti‐inflammatory and antifungal activities of some of the compounds have also been evaluated.