New 4-imino-4H-Chromeno[2,3-d]Pyrimidin-3(5H)-Amine: Synthesis, Cytotoxic Effects on Tumoral Cell Lines and in Silico ADMET Properties

The synthesis of new 4-imino-4H-chromeno[2,3-d]pyrimidin-3(5H)-amine in four steps including one step under microwave dielectric heating is reported. The structural identity of the synthesized compounds was established according to their spectroscopic analysis, such as FT-IR, NMR and mass spectroscopy. These new compounds were tested for their antiproliferative activities on seven representative human tumoral cell lines (Huh7 D12, Caco2, MDA-MB231, MDA-MB468, HCT116, PC3 and MCF7) and also on fibroblasts. Among them, only the compounds 6c showed micromolar cytotoxic activity on tumor cell lines (1.8 50 50 > 25 μM). Finally, in silico ADMET studies ware performed to investigate the possibility of using of the identified compound 6c as potential anti-tumor compound.

Synthesis, Crystal Structure and Antitumor Activity of (E)-4-tert-Butyl-N-(2,4-dichlorobenzylidene)-5-(1,2,4-triazol-1-yl)-thiazol-2-amine

The title compound （E）-4-tert-butyl-N-（2,4-dichlorobenzylidene）-5-（1,2,4-triazol-1-yl）-thiazol-2-amine was synthesized by the reaction of 4-tert-butyl-5-（1,2,4-triazol-1-yl）-thiazol-2-amine with 2,4-dichlorobenzaldehyde, and its crystal structure was determined by singlecrystal X-ray diffraction. The crystal belongs to the triclinic system, space group P1 with a = 7.9748（4）, b = 10.1803（5）, c = 11.4603（6）, α = 102.882（1）, β = 100.253（1）, γ = 104.457（1）°, V = 850.95（7）3, Z = 2, F（000） = 392, C16H15Cl2N5S, Mr = 380.29, Dc = 1.484 g/cm3, S = 1.095, μ = 0.512 mm-1, the final R = 0.0301 and wR = 0.0965 for 3334 observed reflections （I 〉 2σ（I））. The preliminary antitumor activity shows that for the title compound the IC50 of Hela is 0.175 μmol/mL and that of Bel7402 is 0.156 μmol/mL.

Synthesis, Crystal Structure and Antitumor Activity of 4-tert-Butyl-N-(2-fluorophenyl)-5- (1H-1,2,4-triazol-1-yl)-thiazol-2-amine

The title compound has been synthesized by the reaction of 1-bromo-3,3-dime- thyl- 1 - （1 H- 1,2,4-triazol- 1 -yl）butan-2-one with 1 -（2-fluorophenyl）thiourea, and its crystal struc- ture was determined by single-crystal X-ray diffraction. The crystal belongs to the orthorhombic system, space group Pbca with a = 15.2568（6）, b = 12.1533（5）, c = 16.7307（7） A, Z = 8, V = 3102.2（2） A3, Mr = 317.39, Dc = 1.359 g/cm3, S = 1.05, μ = 0.223 mm-1, F（000） = 1328, the final R = 0.034 and wR = 0.097 for 2590 observed reflections （I 〉 2σ（I））. X-ray crystal structure presents the intramolecular N-H…N hydrogen bond, which plays an important role in stabilizing the crystal structure. In addition, the preliminary biological test on the title compound shows good antitumor activity, with IC50 of 0.122 μmol/mL against the Hela cell line.

Synthesis, Crystal Structure and Antitumor Activity of 4-(tert-butyl)-5-(1H-1,2,4-triazol-1-yl)-N-(2-hydroxy-3,5-diiodinebenzyl)-thiazol-2-amine

The title compound, 4-（tert-butyl）-5-（1 H- 1,2,4-triazol- 1 -yl）-N-（2-hydroxy-3,5-diio- dinebenzyl）thiazol-2-amine, was synthesized via the reduction of 4-（tert-butyl）-5-（1H-l,2,4- triazol-l-yl）-N-benzylidene-thiazol-2-amine with NaBH4, and its crystal structure was determined by single-crystal X-ray diffraction. The compound crystallizes in monoclinic system, space group P21/c with a = 7.91944（19）, b = 10.5250（3）, c = 24.4985（6） A, Z = 4, V = 2041.66（9） A3, Mr = 599.22, Dc = 1,949 Mg/m3, S = 1.120, p = 3.203 mm-1, F（000） = 1152, the final R = 0.0283 and wR = 0.0592 for 3490 observed reflections （I 〉 2σ（I））. X-ray analysis displays that the crystal water takes part in three intermolecular hydrogen bonds of O（2）-H（2A）…O（1）, O（2）-H（2B）…N（I） and N（5）-H（5）…O（2）, and an octatomic ring R^（8） is formed via intramolecular hydrogen bond of O（I）-H（IA）…N（4）. Furthermore, the I…I contacts are involved in stabilizing the overall three-dimensional network structure. The preliminary biological test shows the title compound has good antitumor activity with the IC50 value of 26 μM against the Hela cell line.

Synthesis, Crystal Structure and Antitumor Activities of N,N,1-Triphenyl-1H-benzo[d]imidazol-5-amine Derivatives

In order to discover the novel antitumor agents,a series of N,N,1-triphenyl-1Hbenzo[d]imidazol-5-amine derivatives were designed and synthesized,and the structures were characterized by IR,H-RMS,1H and 13C NMR.X-ray crystallography showed that 4c is in monoclinic system,space group P1 with a=9.209(2),b=9.533(3),c=14.097(3)?,β=102.069(3)°,V=1202.2(5)?3,Z=2,F(000)=528,μ=1.74 mm–1,S=1.024,the final R=0.0448 and wR=0.1109.The in vitro antitumor activities of target compounds were evaluated by MTT assay against human cancer cell lines K562,HL-60,HeLa and BGC-823.The target compounds demonstrated weak or moderate antitumor activities against these cell lines.

4-(7-Methoxy-2,2-dimethyl-2,3-dihydrobenzo-furan-5-yl)-N-(pyridin-2-yl)thiazol-2-amine: Chiral Crystal from Achiral Molecule

The title compound 4-（7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl）-N- （pyridin-2-yl） thiazol-2-amine was synthesized by reacting 2-bromo-1-（7-methoxy-2,2-dime- thyl-2,3-dihydrobenzofuran-5-yl）ethanone with 1-（pyridine-2-yl）thiourea, and its crystal was determined by single-crystal X-ray diffraction. The crystal belongs to the monoclinic system, chiral space group C2 with a = 18.1328（14）, b = 5.5969（5）, c = 19.2195（15） A, β= 115.5420（10）°, V= 1759.9（2）A3, Z = 4, F（000） = 744, C19H19N3O2S, Mr= 353.43, Dc= 1.334 g/cm3, S = 1.15, μ = 0.201 mm-1, the final R = 0.035 and wR = 0.111 for 2307 observed reflections （I 〉 2σ（I））. The Flack parameter is -0.03（10）. The preliminary bioassay result indicated that the title compound exhibits strong insecticidal activity （93.75% mortality） against Mythimna separate at the concentration of 1.000 g/L.

Synthesis,Crystal Structure and Antitumor Activity of(E)-N-(4-Fluorobenzylidene)-3-(methylthio)-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazol-4-amine

The crystal structure of the title compound（E）-N-（4-fluorobenzylidene）-3-（methylthio）-5-（3,4,5-trimethoxyphenyl）-4 H-1,2,4-triazol-4-amine（C_（19）H_（19）FN_4O_3S,Mr = 402.44） was synthesized,and its structure was characterized by 1 H-NMR,13 C-NMR,ESI-MS and single-crystal X-ray diffraction.The crystal belongs to the triclinic system,space group P1 with a = 9.228（13）,b = 10.364（14）,c = 10.641（14） ？,α = 85.323（3）,β = 75.172（2）,γ = 80.903（3）°,μ = 0.20 mm^（-1）,M_r = 402.44,V = 970.64（10） ？~3,Z = 2,D_c = 1.377 g/cm^3,F（000） = 420,R = 0.0484 and wR = 0.1474 for 3181 observed reflections with I 〉 2σ（I）.In addition,the preliminary bioassay indicated that the title compound 5 exhibits better inhibitory activity against Hela than 5-fluorouracil.

Selenium-catalyzed oxidative carbonylation of 1,2,3-thiadiazol-5-amine with amines to 1,2,3-thiadiazol-5-ylureas

A facile one-pot, economical approach to 1,2,3-thiadiazol-5-ylureas was developed via seleniumcatalyzed oxidative carbonylation of 1,2,3-thiadiazol-5-amine with a series of amines in one-pot manner in the presence of CO and O_2. This approach is featured with cheap and easily available raw materials,cheap and reusable catalyst selenium, one-pot procedure, high atomic economy, simple operations and no emission of corrosive wastes.

Syntheses, Crystal Structures and Antibacterial Activities of Copper(Ⅱ) and Zinc(Ⅱ) Complexes Based on (E)-4-fluoro-2-((3-morpholinopropylimino)methyl)phenol

Two Schiff base complexes [Cu（L）2] （1） and [Zn（L）2]·3H2O（2） of （E）-4-fluoro-2-（（3-morpholino propylimino）methyl）phenol （HL） have been synthesized and characterized by elemental analysis and single-crystal X-ray diffraction. Crystal data for 1： triclinic, space group Pī with a=4.8000（10）, b=11.109（2）, c=13.921（3）,α=66.55（3）,β=80.35（3）,γ=81.09（3）°, V=668.2（2）3 , Z=1, Dc=1.477g/cm 3 , F（000）=311, and the final R=0.0744 and wR=0.1601 for 2301 observed reflections with I 〉 2σ（I）. And those for 2： monoclinic, space group P21 /c with a=14.789（3）, b=11.713（2）, c=18.846（4）,β=107.85（3）°, V=3107.4（11）3 , Z=4, D c=1.389 g/cm 3 , F（000）=1368, and the final R=0.0749 and wR=0.1348 for 5423 observed reflections with I 〉 2σ（I）. Both 1 and 2 are four-coordinated complexes, with a square-planar geometry of copper（Ⅱ） in 1 and a slightly distorted tetrahedral geometry of zinc（Ⅱ） in 2. An asymmetric unit consists of only one half of a Cu ion and one L ligand in 1, while an asymmetric unit is composed of one Zn ion, two L ligands and three water molecules in 2. Non-classical C-H···O and C-H F hydrogen bonds play important roles in the formation of a 1D chain of 1, but O-H O and O-H N hydrogen bonds play dominant roles in the self-assembly of a 3D network of 2. The antibacterial activities of 1 and 2 against B. subtilis, S. aureus, S. faecalis, P. aeruginosa, E. coli and E. cloacae have been evaluated by MTT method.

Heterocyclization of thiocarbonohydrazides:Facile synthesis of 5-unsubstituted-1,3,4-thiadiazoles

2-（Hydrazinecarbothioyl）-N-substituted hydrazinecarbothioamides react with 2,3,5,6-tetrachloro-1,4-benzoquinone in high yields in a novel fast and facile method to give 5-unsubstituted-1,3,4-thiadiazole-2-amine derivatives.The synthesized compounds were characterized by spectroscopic methods and confirmed by using X-ray crystallography.A rationale for the formation of the products is presented.

Catalyst free synthesis of fused pyrido[2,3-d]pyrimidines and pyrazolo[3,4-b]pyridines in water

A one-pot, three-component condensation reaction of an aldehyde, benzoyl acetonitrile （3-oxo-3-phenylpropane nitrile） and 6- amino-1,3-dimethylpyrimidine-2,4（1H,3H）-dione or 3-methyl-l-phenyl-lH-pyrazol-5-amine in water to give fused pyrido[2,3- d]pyrimidines and pyrazolo[3,4-b]pyridines in high yields without any catalyst, is described.