Synthesis of a novel functionalized tricyclic pyrimidine-fused 1,5-benzodiazepine library

A series of novel tricyclic pyrimidine-fused 1,5-benzodiazepines (PFBZDs) was synthesized using an enaminone-based approach. The key step in the synthetic strategy involves the formation of the CCNMe₂ structure on vicinal carbonyl groups of the 1H-1,5-benzodiazepine-2,4(3H,5H)-dione (BZD). The synthesis of pyrimidine-fused 1,5-benzodiazepines was performed by a simple and efficient method in good to excellent yields under mild and green conditions. The β-enaminoamide intermediates were condensed with thiourea and guanidine derivatives to form the corresponding tricyclic PFBZDs. But reaction of aminoguanidine, thiosemicarbazide, 4-phenylthiosemicarbazide and ethane-1,2-diamine with β-enaminoamides didn't produce any desired product and led to recovery of the corresponding starting BZD.     

苯二氮杂卓类化合物的合成及抗血吸虫活性研究

化合物B30属于苯二氮杂卓类化合物.体外实验表明,在50μM具有100％的杀灭血吸虫效果.本文利用药物化学生物电子等排等原理,设计、合成了4个B30衍生物6、10、13、16,并对其抗血吸虫活性进行初步体外评价.结果显示4个化合物均具有一定的杀虫能力.尤其化合物16有较好的抗血吸虫活性,在50μM浓度下血吸虫的存活率降...     

An efficient solid-phase synthesis of biologically important DNA-interactive pyrrolo[2,1-c][1,4]benzodiazepine dimers (DSB-120) and their C2-fluorinated analogues

A facile method for the solid-phase synthesis of pyrrolo[2,1-c][1,4]benzodiazepine dimers has been developed. p-Nitrophenyl carbonate Wang resin attached to 2-amino-5-methoxy-methyl benzoate has been utilized as the resin-bound starting material and these reactions are monitored by FT-IR spectroscopy of resin beads.     

Solid-phase synthesis of tetrahydro-1,4-benzodiazepin-2-one derivatives

An efficient method for solid-phase construction of tetrahydro-1,4-benzodiazepin-2-one scaffold is described. Polymer-bound 4-(bromomethyl)-3-nitrobenzoic acid was reacted with alpha-amino acid methyl esters, followed by nitro group reduction and hydrolysis. Subsequent intramolecular cyclization and alkylation at N(4) afforded the structurally diverse products in high yields and excellent purities.     

Regioselective alkylation at the N4 positionof a 3-oxo-1,4-benzodiazepine on solid support

An efficient solid phase regioselective alkylation at the N4 positionof a 3-oxo-1,4-benzodiazepine template exemplified by 4-H-2,3,4,5-tetrahydro-7-iodo-3-oxo-1H-1,4-benzodiazepine-2-acetate-polymerester is described. Further chemical elaboration atposition 7, utilizing a modified Heck reaction, allows the incorporationof amides from primary or secondary amines. The two diversity points atpositions 4 and 7 were utilized tosynthesize a 28-membered, combinatorial array on Sasrin® resin in moderate yields and >80% purity. Having validated the chemistry on solid support, acombine and splitapproach to prepare a bead-bound combinatorial library is achievableutilizing similar experimental practices and procedures as in thearray synthesis.     

Mass spectrometric studies of cis‐ and trans‐1a,3‐disubstituted‐1,1‐dichloro‐4‐formyl‐1a, 2,3,4‐tetrahydro‐lH‐azirino[1,2‐a]1,5]benzodiazepines

The mass spectrometric behaviour of four cis‐ and trans‐1a,3‐disubstituted‐1,1‐dichloro‐4‐formyl‐1a,2,3,4‐tetrahydro‐1H‐azirino [1, 2‐a][1,5]benzodiazepines has been studied with the aid of mass‐analysed ion kinetic energy spectrometry and exact mass measurements under electron impact ionization. All compounds show a tendency to eliminate a chlorine atom from the aziridine ring, and then eliminate a neutral propene or styrene from the diazepine ring to yield azirino [1,2‐b][1,3] benzimidazole ions. These azirino [1,2‐a][1,5]‐benzodiazepimes can also eliminate HCl, or Cl plus HCl simultaneously to undergo a ring enlargement rearrangement to yield 1,6‐benzodiazocine ions, which further lose small molecular fragments, propyne or phenylacetylene, with rearrangement to give quinoxaline ions.     

Eco‐friendly synthesis of 3,4‐dihydroquinoxalin‐2‐amine,diazepine‐tetrazole and benzodiazepine‐2‐carboxamide derivatives with the aid of MCM‐48/H5PW10V2O40

A heterogeneous material composed of MCM‐48/H₅PW₁₀V₂O₄₀ was produced and used as an efficient, eco‐friendly and highly recyclable catalyst for the one‐pot and multicomponent synthesis of 3,4‐dihydroquinoxalin‐2‐amine, diazepine‐tetrazole and benzodiazepine‐2‐carboxamide derivatives in aqueous media and at room temperature with high yields in short reaction times (40–60 min). The recoverable catalyst was easily recycled at least five times without any loss of catalytic activity. The structures of obtained products were confirmed using ¹H NMR and ¹³C NMR spectra.     

Fabrication of magnetic zinc adeninate metal–organic frameworks for the extraction of benzodiazepines from urine and wastewater

In this study, an alternative method for synthesizing magnetic cobalt adeninate metal–organic frameworks was developed, and the synthesized materials were examined for their potential application for separating and enriching benzodiazepines from complex samples. Benzodiazepines, widely used as hypnotics, muscle relaxants, sedatives, and anxiolytics, are a class of drugs that require accurate detection and monitoring. Results showed that Fe₃O₄ nanoparticles could be well anchored onto the external surface of cobalt adeninate metal–organic frameworks by using amino‐silane as a linkage. Their adsorption of benzodiazepines was mainly promoted by intermolecular hydrogen binding, π–π interactions and electrostatic attraction. Their potential application was evaluated by extraction of benzodiazepines in urine and wastewater samples prior to liquid chromatography with mass spectrometry. Under optimum conditions, the calibration curves were linear with a correlation coefficient of ≥0.9928 in the concentration range of 10–5000 ng/L for lorazepam and 5–5000 ng/L for estazolam, chlordiazepoxide, alprazolam, midazolam and triazolam. The limits of detection were in the range of 0.71–2.49 ng/L. The percent of extraction recoveries were 80.2–94.5% for urine and 84.1–94.4% for wastewater, respectively. Results suggested that magnetic cobalt adeninate metal–organic frameworks could potentially be a promising material for enriching benzodiazepines from urine and wastewater with high accuracy and precision.     

An Efficient Synthesis of 3H‐1,5‐Benzodiazepine Derivatives Catalyzed by Heteropolyacids as a Heterogeneous Recyclable Catalyst

3H‐1,5‐benzodiazepines were synthesized by the condensation of o‐phenylendiamine and various 1,3‐diketones in the presence of various heteropolyacid (HPA) catalysts under mild conditions in very good yields and with high selectivity.     

Assignment of the 1H and 13C Spectra of 5-Methylthio-4H-1-(p-R1-phenyl)-3a-(p-R2-Phenyl)-3a, 4-dihydro (1,2,4) oxadiazolo(4,5-a), 1, 5-benzodiazepines Using 2D NMR Spectroscopy

The ¹H NMR spectra of the title benzodiazepines derivatives is highly congested because all the protons are in aromatic environment so many proton signals remain overlap even 300 MHz or higher fields. With this in mind, the assignment of the ¹H and ¹³C spectra of these compounds obtained using COSY, NOESY, HMQC and HMBC experiments is reported.