Novel parallel synthesis of N-(4-oxo-2-substituted-4H-quinazolin-3-yl)-substituted sulfonamides

A general method was developed to synthesize a class of N-(4-oxo-2-substituted-4H-quinazolin-3-yl)-substituted sulfonamides in moderate to good yield. This new method can be applied in both single compound and parallel synthesis. About 90 compounds with a variety of substituents were synthesized using this method in a parallel fashion.     

Convenient synthesis of N-(4-(2-aminopyridin-4-yl)thiazol-2-yl)-2-phenylacetamides

We report a facile one-pot, three-step synthesis of N-(4-(2-aminopyridin-4-yl)thiazol-2-yl)-2-phenylacetamides via condensation of 2-p-methoxybenzylamino-4-acetylpyridine with phenylacetylthioureas.     

Nickel(II) and zinc(II) complexes with N-(5,6-dihydro-4H-1,3-thiazin-2-yl)-2-aminobenzimidazole (BzTz): Synthesis,spectral and structural characterization

The reaction of nickel and zinc chlorides and nitrates with the ligand N-(5,6-dihydro-4H-1,3-thiazin-2-yl)-2-aminobenzimidazole (BzTz) leads to the formation of the new complexes: [NiCl₂(BzTz)₂] (1), [Ni(NO₃)(BzTz)₂(H₂O)₃](NO₃) (2), [ZnCl₂(BzTz)₂] (3) and [Zn(NO₃)₂(BzTz)₂] (4). They have been characterized by spectroscopic methods (electronic, infrared and NMR) and magnetic susceptibility measurements. Additionally, the crystal structures of the complexes 1 and 3 have been determined by X-ray single-crystal diffraction. The ligand exhibits the N-benzimidazole coordination mode on interacting with the metal centers. The X-ray structure of the complexes 1 and 3 reveals a distorted tetrahedral coordination geometry around the metal center, with the metallic atoms coordinated to two chlorine atoms and two benzimidazole nitrogen atoms. These two complexes are isostructural, crystallizing in the monoclinic system and Cc space group. In complex 2 the geometry around the nickel atom could be described as a distorted octahedron whereas in case of complex 4 the zinc atom is in a distorted tetrahedral environment.     

Base-mediated one-pot synthesis of 3,4,5,6-tetrahydro-4-substituted benzo[h]quinazoline-2(1H)-thione derivatives and evaluation of their antioxidant activity

One-pot three-component Beginelli-like reactions of a ketone 1, an aryl aldehyde 2, and thiourea 3 in the presence of sodium hydroxide are described. In this reaction, 3,4,5,6-tertrahydro-4-substituted quinazoline-2(1H)-thione derivatives 4a–h were obtained in good yields (73–85%). The compound 4a has been characterized by single crystal X-ray analysis. All the synthesized compounds 4a–h and 5a–b were screened for their in vitro antioxidant activity. Compounds 4c, 4e, and 4h have exhibited an excellent than the standard ascorbic acid. Compounds 4d, 4f, and 4g have also shown good activity. Remaining compounds show moderate antioxidant activity.     

An efficient solvent-tuning approach for the rapid synthesis of thiazolidinone derivatives and the selective synthesis of 2-amino-4H-1,3-thiazin-4-one and dimethyl 3,3′-thiodiacrylates

Green synthetic approach has been developed for the rapid generation of thiazolidinone derivatives as crystallized products under catalyst-free conditions in water by polarity adjustment with ethyl lactate as a co-solvent in excellent yields. Additionally, interesting findings on the selective synthesis of 2-amino-4H-1,3-thiazin-4-one and dimethyl 3,3′-thiodiacrylates have been reported.     

A novel synthesis of N-(piperidin-4-yl)-1,3-dihydroindol-2-one via an intramolecular Pd-catalyzed amination

A novel efficient synthetic route to the pharmaceutical key intermediate N-(piperidin-4-yl)-1,3-dihydroindol-2-one is described. The key step involves a high-yielding intramolecular palladium-catalyzed amination reaction using Buchwald’s X-Phos ligand under mild reaction conditions.     

Convenient method for the synthesis of some novel chiral methyl 2-(2-oxo-2H-benzo[e][1,3]oxazin-3(4H)-yl)propanoate derivatives and biological evaluation of their antioxidant,cytotoxic, and molecular docking properties

Ten chiral methyl 2-(2-oxo-2H-benzo[e][1,3]oxazin-3(4H)-yl)propanoate derivatives 6a-6j have been synthesized from optically pure amino methyl phenol 5 and 4-nitrophenyl chloroformate. These derivatives 6a-6j are characterized by ¹H NMR, ¹³C NMR, FT-IR, and HRMS spectral techniques. Optical purity of these derivatives was confirmed by chiral HPLC method. Ten synthesized ester derivatives 6a-6j were screened for their in vitro antioxidant activity. Among the compounds 6b-d and 6h-j have exhibited comparable antioxidant activity with ascorbic acid as a standard. Compounds 6a and 6e-g have shown moderate antioxidant activity. Further, the in vitro cytotoxicity of these compounds were studied through MTT cell proliferation assay in addition the effect on LDH leakage and NO release. Among the derivatives, 6j showed extremely best activity and the IC₅₀ value (12.54 ± 0.71 μM) is very close to doxorubicin (7.2 ± 0.58 μM) as a standard. Compounds 6b , 6h , and 6i showed better inhibition next to compound 6j on the viability of HepG2 cells with an IC₅₀ value (μM) of 56.02 ± 1.4, 41.76 ± 0.58, and 38.17 ± 0.34, respectively. Also, molecular docking studies have been carried out with STAT-3 (PDB ID: 1BG1) and BCL-2 (PDB ID: 4AQ3) proteins against the four active compounds 6b , 6h , 6i , and 6j . The binding energies of the tested compounds were in the range of −7.76 to −8.41 kcal/mol, which is very close to doxorubicin (−8.53 kcal/mol) as a standard. These molecular docking results are in good agreement with the in vitro studies.     

New copper complexes with N-(5,6-dihydro-4H-1,3-thiazin-2-yl)benzamide ligand

Crystals of two copper complexes with N-(5,6-dihydro-4H- +1,3-thiazin-2-yl)benzamide were obtained and characterized by X-ray diffraction analysis. LETDI studies have shown that the composition of the complex is inhomogeneous, and the precipitated crystals can have different structures being of Cuii or Cui–Cuii types. The complexes are significantly more cytotoxic toward the leukemic Jurkat cell line than to healthy lymphocytes.     

synthesis and some transformations of 4-oxo-2-(β-ethoxyvinyl)-4H-1,3-benzoxazinium salts

A method was developed for the synthesis of 4-oxo-(-ethoxyvinyl)-4H-1,3-benzoxazinium salts by condensation of oxo-2-alkylbenzoxazinium salts by condensation of oxo-2-alkylbenzoxazinium salts with ethyl orthoformate. During hydrolysis and aminolysis, attack of the nucleophile is directed to the -carbon atom of the benzoxazinium salts. The previously unknown 2-formylmethylene-4-oxo-3,4-dihydro-2H-1,3-benzoxazines and their nitrogen derivatives were obtained.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 322–327, March, 1977.     

Synthesis and antimicrobial activity of some derivatives of (7-hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid hydrazide

(7-Hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid hydrazide (2) was prepared from (7-hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid ethyl ester (1) and 100% hydrazine hydrate. Compound 2, is the key intermediate for the synthesis of several series of new compounds such as Schiff's bases 3a-l, formic acid N'-[2-(7-hydroxy-2-oxo-2H- chromen-4-yl)acetyl] hydrazide (4), acetic acid N'-[2-(7-hydroxy-2-oxo-2H-chromen-4- yl)-acetyl] hydrazide (5), (7-hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid N'-[2-(4- hydroxy-2-oxo-2H-chromen-3-yl)-2-oxoethyl] hydrazide (6), 4-phenyl-1-(7-hydroxy-2- oxo-2H-chromen- 4-acetyl) thiosemicarbazide (7), ethyl 3-{2-[2-(7-hydroxy-2-oxo-2H- chromen-4-yl)-acetyl]hydrazono}butanoate (8), (7-hydroxy-2-oxo-2H-chromen-4-yl)- acetic acid N'-[(4-trifluoromethylphenylimino)methyl] hydrazide (9) and (7-hydroxy-2- oxo-2H-chromen-4-yl)acetic acid N'-[(2,3,4-trifluorophenylimino)-methyl] hydrazide (10). Cyclo- condensation of compound 2 with pentane-2,4-dione gave 4-[2-(3,5- dimethyl-1H-pyrazol-1-yl)-2-oxoethyl]-7-hydroxy-2H-chromen-2-one (11), while with carbon disulfide it afforded 7-hydroxy-4-[(5-mercapto-1,3,4-oxadiazol-2-yl)methyl]-2H- chromen-2-one (12) and with potassium isothiocyanate it gave 7-hydroxy-4-[(5- mercapto-4H-1,2,4-triazol-3-yl)methyl]-2H-chromen-2-one (14). Compound 7 was cyclized to afford 2-(7-hydroxy-2-oxo-2H-chromen-4-yl)-N -(4-oxo-2-phenylimino- thiazolidin-3-yl) acetamide (15).     

Convenient synthesis of novel N-(5-allyl-7,7-difluoro)-4,5,6,7-tetrahydro-2H-indazol-3-yl)-carboxymides

5-Allyl-7,7-difluoro-2-(2,4-difluorophenyl)-6-(4-methoxyphenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-3-amine represents a fluorinated heterocyclic scaffold, potentially attractive. It was synthesized via Michael addition, Mannich reaction of the difluorinated ethyl bromoacetate with a benzotriazole derivative, followed by a Dieckmann condensation. Starting from simple materials, this efficient route which gives access to novel functionalized N-(5-allyl-7,7-dihalo)-4,5,6,7-tetrahydro-2H-indazol-3-yl)-carboxymides, was explored and adapted for parallel synthesis, resulting in a compound library.     

A one-pot synthesis of 3,3′-methylenebis(2-arylamino-4H-chromen-4-one) from C-(4-oxo-4H-1-benzopyran-3-yl)-N-arylnitrone

2-(Arylamino)-4-oxo-4H-chromene-3-carbaldehyde 3 (R² = aryl) produces 12H-chromeno[2,3-b]quinolin-12-one 4 when treated with sarcosine, piperidine or diethylamine, but produces 3,3′-methylenebis(2-arylamino-4H-chromen-4-one) 8 when treated with the same amine in the presence of an excess of formaldehyde. Compound 3 (R² = alkyl) was found to be less reactive than the N-aryl analogues towards the deformylative Mannich-type reaction.     

The synthesis and properties of some derivatives of 2-oxo-4-thioxo- and 2, 4-dithioxo-1h, 3h-pteridines

Some new derivatives of 2-oxo-4-thioxo- (I) and 2,4-dithioxo-1H, 3H-pteridine (II) have been prepared by treatment of 2,4-dioxo- (III) and 2-thioxo-4-oxo-1H,3H-pteridines (IV) with P₂S₅ in dioxane solution. The corresponding 4-phenylhydrazones, and the products of reaction of the pteridinethiones with aliphatic and aromatic amines and amino acids, have been obtained.     

Synthesis and anticancer activity evaluation of 3-(4-oxo-2-thioxothiazolidin-5-yl)-1H-indole-carboxylic acids derivatives

Abstract

A mild and efficient method for the synthesis of 1-oxo-9H-thiopyrano[3,4-b]indole-3-carboxylic acids and dimerized 3-(4-carboxy-1H-3-indolyl)-2-propenoic acids via alkaline hydrolysis of 3-(rhodanin-5-yl)-1H-indole-2-carboxylic acids derivatives was elaborated. Anticancer activity screening in NCI60-cell lines assay allowed identification of 5-fluoro-3-(4-oxo-2-thioxothiazolidin-5-ylidenemethyl)-1H-indole-2-carboxylic acid methyl ester 2a with significant antimitotic activity at micromolar and submicromolar concentrations.     

beta-Pseudopeptide foldamers. The homo-oligomers of (4R)-(2-oxo-1,3-oxazolidin-4-yl)-acetic acid (D-Oxac)

A total synthesis in solution and a conformational analysis of the homo-oligomers of (4R)-(2-oxo-1,3-oxazolidin-4-yl)-acetic acid (D-Oxac) to the tetramer level are described. As the D-Oxac building block contains both an oxazolidin-2-one and a beta-amino acid group, it may represent a new type of conformationally constrained tool for the construction of beta-pseudopeptide foldamers. A conformational investigation using NMR and an extensive, unconstrained analysis with a Monte Carlo search to the octamer level, both in water and in chloroform, showed that these homo-oligomers tend to fold in a regular helical structure in a competitive solvent, such as water. Since aqueous solutions are of major relevance for biological systems, these molecules are good candidates for application to these environments.