Radiosynthesis and Evaluation of Cyclohexyl (5-(2-[11C-Carbonyl]acetamidobenzo[d]thiazol-6-yl)-2-Methylpyridin-3-yl)Carbamate ([11C]PK68) As a New Radioligand For Imaging Receptor-Interacting Protein 1 Kinase

Background: Receptor-interacting protein 1 kinase (RIPK1) is a key enzyme in the regulation of cellular necroptosis. Recently, cyclohexyl (5-(2-acetamidobenzo[d]thiazol-6-yl)-2-methylpyridin-3-yl)carbamate (PK68, 5) has been developed as a potent inhibitor of RIPK1. Herein, we radiosynthesized [11C]PK68 as a new positron emission tomography (PET) ligand for imaging RIPK1 and evaluated its potential in vivo.Results: We synthesized [11C]PK68 by reacting amine precursor 14 with [11C]acetyl chloride. At the end of synthesis, we obtained [11C]PK68 of 1200–1790 MBq (n = 10) with >99% radiochemical purity and a molar activity of 37–99 GBq/μmol starting from 18–33 GBq of [11C]CO2. The fully automated synthesis took 30 min from the end of irradiation. In a small-animal PET study, [11C]PK68 was rapidly distributed in the liver and kidneys of healthy mice after injection, and was subsequently cleared from their bodies via hepatobiliary excretion and the intestinal reuptake pathway. Although there was no obvious specific binding of RIPK1 in the PET study, [11C]PK68 demonstrated relatively high stability in vivo, and may be used as a lead compound for further candidate development.Conclusions: In the present study, we successfully radiosynthesized [11C]PK68 and evaluated its potential in vivo. We are planning to optimize the chemical structure of [11C]PK68 and conduct further PET studies on it using pathological models.

Theophylline Derivatives' In-vivo Analgesic and Anti-Inflammatory Activities

The reaction of theophylline and chloro-acetyl chloride produced an exceptional series of substituted theophylline derivatives (3A-3D), followed by ammonium thiocyanate and substituted aromatic aldehyde, and these synthesized derivatives were screened to study their analgesic and anti-inflammatory activities. UV, IR, H-1 NMR, mass spectral data, and CHN activities were used to describe the compounds, which were shown to be considerably efficacious at 100 mg/kg p.o., as well as experimental results that were statistically significant at the p <0.01 and p <0.05 levels.

Synthesis and Antioxidant Properties of Novel 2-(2,4-Dioxothiazolidin-5-ylidene)-Acetamides Containing 1,3,4-Thia/Oxadiazole Moieties

A series of novel 1,3,4-thia(oxa)diazole substituted 2-(2,4-dioxothiazolidine-5-ylidene)-acetamides 3a-c, 4 and 5a-k have been synthesized following the acylation reaction of 2-amino-5-aryl-1,3,4-oxadiazoles, 5-amino-1,3,4-thiadiazole-2-thiol and it’s S-alkylated derivatives with 2-(2,4-dioxothiazolidine-5-ylidene)acetyl chloride in dioxane medium. The functionalization of compounds 3b, 3c, 5d and 5e was carried out on their N3 position under N-alkylation conditions with N-aryl-2-chloroacetamides in DMF/ethanol medium yielded the corresponding 2,4-dioxothiazolidine-3,5-diacetic acid diamides 6a-e and 7a-b. The structures of target compounds were confirmed by using 1H NMR spectroscopy and elemental analysis. The antioxidant activity evaluation in vitro of the synthesized compounds was performed by the method of scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. As a result, the highly active compound 4, namely 2-(2,4-dioxothiazolidin-5-ylidene)-N-(5-mercapto-[1,3,4]thiadiazol-2-yl)acetamide was found to be the most efficient candidate among all compounds with a radical scavenging ability of 88.9%, which was comparable that for ascorbic acid (92.7%). The experimentally calculated IC50 value of 43.1 µM for compound 4 was lower than for ascorbic acid (50.5 µM).

SYNTHESIS AND MOLECULAR DOCKING ANALYSIS OF OXAZETIDINE DERIVATIVES FOR NEUROLOGICAL DISORDERS

A series of Oxazetidine (NL1-NL12) from reacting tryptophan and aromatic aldehydes were synthesized in good yields by involving 2-{[(4-chlorophenyl) methylidene] amino}-3-(1H-indol-3-yl) propanoic acid and chloro acetyl chloride as reactive intermediates. All the synthesized derivatives were screened via spectral techniques. Synthesized molecules were virtually screened against Human A2A Adenosine receptor interactions analysis using molecular docking to elucidate CNS potential. Synthesized derivatives showed excellent binding towards the Human A2A Adenosine receptor.

Benzofuran-oxadiazole hybrids: Design, Synthesis and antimicrobial activity studies

The six benzofuran-oxadiazole derivatives (4a-d) and (5a-b) have been designed, synthesized, characterized and evaluated for antimicrobial activity. The key synthetic intermediate 5-bromo-N'-hydroxybenzofuran -2-carboxamidine (3) was prepared from 5-bromobenzofuran-2-carboxylic acid (1) in two consecutive steps involving reaction with NaN3, in presence of TEA, Xtalfluor-E, PPh3 in dry DCM at 0oC followed by the treatment of resulting carbonitrile (2) with hydroxylamine hydrochloride in presence of sodium methoxide under reflux in aqueous ethanol. Reaction of carboxamidine (3) with different aryl esters in presence of K2CO3 under reflux conditions in toluene afforded 3-(5-bromobenzofuran-2-yl)-5-substituted phenyl-1,2,4-oxadiazoles (4a-d) while the refluxion of a solution of carboxamidine (3) in dichloromethane with chloro/bromo acetyl chloride in presence of TEA and a catalytic amount of HBTU furnished 3-(5-bromobenzofuran-2-yl)-5-(chloromethyl)-1,2,4-oxadia zole (5a) and 3-(5-bromobenzofuran-2-yl)-5-(bromomethyl)-1,2,4-oxadiazole (5b).

Friedel-Crafts acylation of antiaromatic norcorrole: electronic and steric modulation of the paratropic current

Acyl chlorides react with norcorrolatonickle(II) in dichloromethane in the presence of AlCl3 at room temperature affording two isomeric monoketone derivatives in moderate yields. For acetyl chloride, also diketones were detected...

Synthesis and Characterization of some new Ibuprofen Derivatives and Study Antibacterial Activity

The series of ibuprofen compounds (1–5) have been synthesized. Acid chloride (4-isobutylphenyl) acetyl chloride (1) was obtained from interaction ibuprofen with thionyl chloride, this compound (1) was treated with hydrazine to give acid hydrazide 2-(4-isobutylphenyl) acetohydrazide (2). Schiff’s base of 2-(4-isobutylphenyl) acetohydrazide derivatives (3a–e) were prepared by refluxing (2) with different aromatic aldehydes and ketones. The (4-isobutylphenyl) acetyl chloride (1) converts to esters (4a–f) by reacting with alcohols, and with secondary amines to give amide compounds of (4-isobutylphenyl) acetyl chloride (5a–b). All structures of synthesized compounds have been confirmed by elemental analysis (C, H, and N) and spectral data (FT-IR and 1H NMR). The prepared compounds (3a–e) and (4a–f) have been screened for their antibacterial activity for S. aureus, B. subtilis, E. coli, P. aeuroginosa, and were shown to have antibacterial activity.

An Efficient Catalytic Method for the C-N Acylation of Heterocycles by Schiff Base Co(II), Ni(II), Cu(II) and Zn(II) Transition Metal Complexes..

: The catalytic activity of Schiff base Co(II), Ni(II), Cu(II) and Zn(II) transition metal complexes were tested for N-Acylation of heterocycles with acetyl chloride. It is observed that all the complexes worked as the efficient catalysts. The Structural type of the complexes were studied by X-ray powder diffractogram (XRD). The mixed ligand complexes with PPh3 ligand show greater activity as compared to Phen complexes and Schiff base complexes. Especially complex [Ni(L)(PPh3)2Cl2] efficiently worked as catalyst because of high thermal stability (TGA-DSC) and large catalytic surface area (BET).