Design and Synthesis of 3‐Aryl‐5‐Alicylic‐[1,2,4]‐oxadiazoles as Novel Platelet Aggregation Inhibitors

A series of 4‐[2‐(alicyclic‐[1,2,4]oxadiazol‐3‐yl)phenoxy]‐butyric acids were synthesized from N‐hydroxy‐2‐isopropoxy benzamidine in 4 steps with good yields. These [1,2,4]oxadiazoles are novel platelet aggregation inhibitors preventing human platelet aggregation induced by thromboxane derivative U44,619 and adenosine diphosphate. A structure‐activity‐relationship study revealed that the potency for these 5‐oxadiazoles increases with the increase in the ring size of the alicylic rings. Derivative 8f may be useful as a template for the design of more potent anti‐platelet agents.     

Synthesis of Novel 3‐Acetyl‐2‐Aryl‐5‐(3‐Aryl‐1‐Phenyl‐Pyrazol‐4‐yl)‐2,3‐Dihydro‐1,3,4‐Oxadiazoles

A series of novel pyrazolyl‐substituted 1,3,4‐oxadiazole derivatives ( 4a‐4o ) were prepared by cyclization of the intermediate N′‐((3‐aryl‐l‐phenyl‐pyrazol‐4‐yl)methylene)arylhydrazide with acetic anhydride. The structures of the new compounds were confirmed by IR, ¹H NMR, MS and elemental analysis. Furthermore, preliminary bioassay of some of the title compounds indicated that they exhibited moderate inhibition against HIV‐1 PR.     

Δ3- and Δ4-1,2,4-oxadiazolin-5- and 3-ones

Preparations for 2,3-diphenyl- and 2-benzyI-3-phenyl-Δ³-1,2,4-oxadiazolin-5-ones (3) and (4) and for 2,5-diphenyl-Δ⁴-1,2,4-oxadiazolin-3-one ( 7 ) are reported.     

Synthesis of Novel Biphenyltetrazole Derivatives Containing 5‐Methylisoxazole Substituted 1,2,4‐Triazole

An efficient route to synthesize the target compounds was developed. Fifteen new 5‐[4′‐(5‐isoxazol‐4‐aryl‐1,2,4‐triazol‐3‐yl‐sulfanylmethyl)‐biphenyl‐2‐yl]‐tetrazoles derivatives were synthesized. The structures of the new compounds synthesized were confirmed by elemental analyses and spectral data.     

Design,Synthesis, and Herbicidal Activities of 3‐Aryl‐4‐substituted‐5‐[3‐(trifluoromethyl)phenoxy]‐1,2,4‐triazoles

In order to find novel bleaching herbicide lead compounds, a series of novel 3‐aryl‐4‐substituted‐5‐[3‐(trifluoromethyl)phenoxy]‐1,2,4‐triazoles were designed and synthesized by the multi‐step reactions. N‐(Arylformamido)phenylthioureas undergo ring closure in the presence of sodium hydroxide to generate 3‐aryl‐4‐substituted‐4H‐[1,2,4]triazol‐5‐thiols 1 , which reacted with methyl sulfate in the presence of K₂CO₃ to give 3‐aryl‐5‐methylsulfanyl‐4‐substituted‐4H‐[1,2,4]triazoles 2 . The target compounds 4 were synthesized by the oxidation of 2 in the presence of H₂O₂ and Na₂WO₄, followed by the substitution with 3‐(trifluoromethyl)phenol in moderate to good yields. Their structures were confirmed by IR, ¹H NMR, EI–MS, and elemental analyses. The preliminary bioassay indicated that some of them displayed moderate to good selective herbicidal activity against Brassica campestris L at the concentration of 100 µg/mL. Compounds 4c and 4i possessed 75.0% and 82.6% inhibition against Brassica campestris L at the concentration of 100 µg/mL. However, the target compounds 4 showed weak herbicidal activity against Echinochloa crus‐galli at the concentration of 100 and 10 µg/mL.     

A Rapid and Convenient Synthetic Route to Novel 1,5-Benzodiazepine Derivatives of 5-Methyl-3-phenyl-2-oxo-Δ4-1,3,4-oxadiazolines from p-Acetylphenylsydnone and Their Pharmacological Activity

A simple and high yielding method for the integration of 1,5-benzodiazepines integrated with 5-methyl- 2-oxo-3-phenyl-△^4-1,3,4-oxadiazolines in 75%-90% yield by microwave irradiation is devised. Microwave-accelerated reaction was compared with thermal method. All the compounds were characterized by physical, analytical and spectral （IR, 1^H NMR, MS） data. Title compounds were screened for preliminary pharmacological activities.     

A Novel Synthesis of Bis-（1,2,4-triazolyl）-3-disulfides

Manganese triacetate was introduced as a new reagent for radical cyclization of substituted aminothioureas. Bis-（1,2,4-triazolyl）-3-disulfides were generated in 10 min under microwave irradiation.     

Synthesis of Racemic Δ3‐2‐Hydroxybakuchiol and Its Analogues

The first synthetic approach to (±)‐Δ³‐2‐hydroxybakuchiol (=4‐[(1E,5E)‐3‐ethenyl‐7‐hydroxy‐3,7‐dimethylocta‐1,5‐dien‐1‐yl]phenol; 14 ) and its analogues 13a – 13f was developed by 12 steps (Schemes 2 and 3). The key features of the approach are the construction of the quaternary C‐center bearing the ethenyl group by a Johnson–Claisen rearrangement (→ 6 ); and of an (E)‐alkenyl iodide via a Takai–Utimoto reaction (→ 11 ); and an arylation via a Negishi cross‐coupling reaction (→ 12e – 12f ).     

Synthesis of 6‐Aryl‐4H‐imidazo[1,2‐b][1,2,4]triazoles and 6‐Aryl‐thiazolo[3,2‐b][1,2,4]triazoles

The cyclization of the derivatives of 3‐aminotriazole, 2‐(5‐substituted 4H‐1,2,4‐triazol‐3‐ylamino)‐1‐arylethanones and 2‐(4H‐1,2,4‐triazol‐3‐ylthio)‐1‐arylethanones to yield 6‐aryl‐4H‐imidazo[1,2‐b][1,2,4]triazoles and 6‐aryl‐thiazolo[3,2‐b][1,2,4]triazoles has been described.     

Three‐Step Synthesis of Novel 2‐Aryl‐3‐benzamidobenzofurans: Regiospecific Reactions Catalyzed by Molybdate Sulfuric Acid

A solvent‐free and synthetic pathway to novel benzofuran derivatives, starting from oxidation of phenyl ketones to arylglyoxals in three steps was developed. The molybdate sulfuric acid catalyzed the reaction of arylglyoxals with benzamide and phenols to afford 2‐aryl‐3‐benzamidobenzofurans in high yield. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, ¹H NMR, and ¹³C NMR spectral data. The present methodology offers several advantages such as non‐hazardous reaction condition, simple operation, and work‐up procedure.     

Catalytic Enantioselective Synthesis of a 3‐Aryl‐3‐benzyloxindole (=3‐Aryl‐3‐benzyl‐1,3‐dihydro‐2H‐indol‐2‐one) Exhibiting Antitumor Activity

A palladium‐catalyzed intramolecular α‐arylation of an amide in the presence of a bulky chiral N‐heterocyclic carbene ligand is the key step in the first catalytic synthesis of (3R)‐6‐chloro‐3‐(3‐chlorobenzyl)‐1,3‐dihydro‐3‐(3‐methoxyphenyl)‐2H‐indol‐2‐one ((R)‐ 5 ). This oxindole, in racemic form, had been shown previously to be an anticancer agent. (R)‐ 5 was obtained with an overall yield of 45% and with 96% enantioselectivity.     

3‐Aryl‐5‐furylpyrazolines and their biological activities

Aryl‐furyl substituted pyrazolines 2a–c and 4a–c were prepared by the reaction of α,β‐unsaturated carbonyl compounds with hydrazine or phenyl hydrazine. N‐chloroacetyl derivatives 3a–c were obtained by the N‐acetylation of 2a–c . The antibacterial activities of synthesized pyrazolines were examined by employing the disk‐diffusion technique. All synthesized compounds showed antibacterial effects in 1200 μg concentration. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:345–347, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10159     

Novel Synthesis of 2‐Aryl‐4,5,6,7‐tetrahydro‐1,2‐benzisothiazol‐3(2H)‐ones and Their S‐Oxides

2‐Aryl‐4,5,6,7‐tetrahydro‐1,2‐benzisothiazol‐3(2H)‐ones 1a – e were synthesized by cyclocondensation of 2‐(thiocyanato)cyclohexene‐1‐carboxanilides 9 as a convenient new method. Their S‐oxides 10 were prepared by two routes, either by oxidation of 1 or dehydration of rac‐cis‐3‐hydroperoxysultims 11 . Furthermore, compounds 1 have been identified by HPLC? API‐MS‐MS as intermediates in the oxidation process of the salts 6 . The hydroperoxides 12b and rac‐trans‐ 11b have been unambiguously detected by HPLC? MS investigations and in the reaction of rac‐cis‐ 13b with H₂O₂ to the hydroperoxides rac‐trans‐ 11b and rac‐cis‐ 11b .     

Synthesis and Molecular Structure of New S‐Nucleosides of 5‐(4‐Pyridyl)‐4‐Aryl‐4H‐1,2,4‐Triazole‐3‐Thiols

The synthesis of some new S‐nucleosides of 5‐(4‐pyridyl)‐4‐aryl‐4H‐1,2,4‐triazole‐3‐thiols ( 4a‐n ) is described. Direct glycosylation of ( 4a‐n ) with tetra‐O‐acetyl‐α‐D‐glucopyranosyl bromide in the presence of potassium hydroxide followed by deacetylation using dry ammonia in methanol gave the corresponding 3‐S‐(ñ‐D‐glucopyranosyl)‐5‐(4‐pyridyl)‐4‐aryl‐4H‐1,2,4‐triazoles ( 6a‐n ) in good yields. All the compounds were fully characterized by means of ¹HNMR, ¹³C NMR spectra and elemental analyses. To assist in the interpretation of the spectroscopic data, the crystal structure of 3‐S‐(2′,3′,4′,6′‐tetra‐O‐acetyl‐β‐D‐glucopyranosyl)‐5‐(4‐pyridyl)‐4‐phenyl‐4H‐1,2,4‐triazole ( 5a ) was determined by X‐ray diffraction.     

Synthesis of Novel 1,2,4‐Triazole‐3‐thione Derivatives as Influenza Neuraminidase Inhibitors

A series of 1,2,4‐triazole‐3‐thione derivatives ( 6a – 6t ) were synthesized and evaluated against influenza viruses (H1N1) neuraminidase (NA) in vitro. Eighteen compounds exhibited inhibitory potency with IC₅₀ values ranging from 14.68 ± 0.49 to 39.85 ± 4.23 μg/mL. Among them, compounds 6e and 6h showed significant inhibitory activity with IC₅₀ values of 14.97 ± 0.70 and 14.68 ± 0.49 μg/mL, respectively. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction between active compounds and NA.     

Asymmetric Synthesis of 2,4,5‐Trisubstituted Δ2‐Thiazolines

Δ²‐Thiazolines are interesting heterocycles that display a wide variety of biological characteristics. They are also common in chiral ligands used for asymmetric syntheses and as synthetic intermediates. Herein, we present asymmetric routes to 2,4,5‐trisubstituted Δ²‐thiazolines. These Δ²‐thiazolines were synthesized from readily accessible/commercially available α,β‐unsaturated methyl esters through a Sharpless asymmetric dihydroxylation and an O→N acyl migration reaction as key steps. The final products were obtained in good yields with up to 97 % enantiomeric excess.     

Synthesis,Characterization and Crystal Structure of 4‐Amino‐1,2,4‐Δ2‐triazoline‐5‐thione and its Silver(I) Complex

The reaction of 4‐amino‐1,2,4‐Δ²‐triazoline‐5‐thione (ATT, 1 ) with AgNO₃ in methanol led to the complex [Ag(ATT)₂]NO₃ ( 2 ). 2 was characterized by elemental analyses, ¹H NMR, IR, and Raman spectroscopy as well as single‐crystal X‐ray diffraction. The molecular structure of 1 was also determined by single crystal X‐ray analysis. Crystal data for 1 at ?80 C: space group C2/c with a = 2107.4(2), b = 1425.1(1), c = 688.4(1) pm, β = 104.55(1)°, Z = 16, R₁ = 0.0514, crystal data for 2 at ?80 °C: space group P2₁/c with a = 675.7(1), b = 1321.1(1), c = 1311.2(1) pm, β = 90.03(1)°, Z = 4, R₁ = 0.0437.     

Synthesis and structure of substituted 5‐phenoxy‐1,2,4‐dithiazole‐3‐ones

Seven new substituted 5‐phenoxy‐1,2,4‐dithiazole‐3‐ones were prepared in modest yield (53–76%) from corresponding O‐phenyl thiocarbamates and chlorocarbonylsulfenyl chloride in dry ether at ?10 °C. All of the compounds were characterized by NMR and elemental analysis and some of them by X‐ray diffraction. Preliminary kinetic measurements showed that the parent 5‐phenoxy‐1,2,4‐dithiazole‐3‐one is a very efficient sulfurizing agent toward triphenyl phosphite. J. Heterocyclic Chem., (2011)     

Synthesis of 3‐Halogenated Flavonoids via Electrophile‐Promoted Cyclization of 2‐(3‐Aryl‐2‐propynoyl)anisoles

Treatment of 2‐(1‐aryl‐3‐propynoyl) anisoles 1 with N‐chlorosuccinimide (NCS) or N‐bromosuccinimide (NBS) gave the 3‐halogenated flavones and their related molecules in moderate yields.