Assembly of Benzothiazine and Triazole in a Single Molecular Entity: Synthesis of -Oxicam Derived Novel Molecules as Potential Antibacterial/ Anti-cancer Agents.

Background: Benzothiazine derivatives, because of their various biological activities have attracted particular attention in Med Chem and drug discovery efforts. The synthetic modifications of 1,2-benzothiazine 1,1-dioxides have been undertaken in order to explore and identify novel compounds or new analogues possessing promising biological activities. In our effort we have designed -oxicam derived bezothiazine-1,2,3-triazole derivatives as potential antibacterial agents.

1H-1,2,3-Triazolyl-substituted 1,3,4-oxadiazole derivatives containing structural features of ibuprofen/naproxen: Their synthesis and antibacterial evaluation.

1H-1,2,3-Triazolyl-substituted 1,3,4-oxadiazole derivatives containing structural features of ibuprofen/naproxen were synthesized for the first time using a Cu catalyzed azide-alkyne cycloaddition (CuAAC) strategy. An optimized reaction condition was established for this purpose and twenty new compounds were synthesized using this methodology. Several of these compounds showed good to reasonable antibacterial activities when tested against three gram-positive and three gram-negative species.

Application of response surface method to evaluate the cytotoxic potency of Ulva fasciata Delile, a marine macro alga.

Bioprospecting of marine natural products has recently produced a substantial number of drug candidates. Ulva fasciata Delile, belonging to the family Ulvaceae, is a green marine macro alga that grows profusely on the coastal seashore of South India. In the present study, we investigated the in vitro cytotoxic potential of a methanolic extract of U .

Synthesis, anticonvulsant, sedative and anxiolytic activities of novel annulated pyrrolo[1,4]benzodiazepines.

Four new pentacyclic benzodiazepine derivatives (PBDTs 13-16) were synthesized by conventional thermal heating and microwave-assisted intramolecular cyclocondensation. Their anticonvulsant, sedative and anxiolytic activities were evaluated by drug-induced convulsion models, a pentobarbital-induced hypnotic model and an elevated plus maze in mice. PBDT 13, a triazolopyrrolo[2,1-c][1,4]benzodiazepin-8-one fused with a thiadiazolone ring, exhibited the best anticonvulsant, sedative and anxiolytic effects in our tests.

Estimation of enantiomeric impurity in piperidin-3-amine by chiral HPLC with precolumn derivatization.

A simple, precise, accurate, robust chiral high-performance liquid chromatographic (chiral HPLC) method was developed for estimation of (S)-piperidin-3-amine (S-isomer) in (R)-piperidin-3-amine dihydrochloride (R-AMP). As AMP is a high-melting solid and nonchromophoric compound, development of a suitable chiral method is a challenging task. The proposed chiral HPLC-UV method involves a precolumn derivatization technique with para toluene sulphonyl chloride (PTSC) in the presence of a base to introduce chromophore into analytes.

Stability-Indicating UPLC Method for Tramadol HCl Impurities in the Tramadol Injection after Dilution by Infusion Fluids (5% Dextrose and 0.9% Sodium Chloride).

A novel, rapid, and sensitive ultra-performance liquid chromatography (UPLC) method has been developed and validated as per ICH guidelines for the determination of tramadol HCl impurities in the tramadol HCl injection after reconstitution by infusion fluids (5% dextrose and 0.9% sodium chloride). The tramadol HCl injection is for the treatment of patients with moderate-to-severe pain.

Synthesis of 2,2,4-trimethyl-1,2-dihydroquinolinyl substituted 1,2,3-triazole derivatives: their evaluation as potential PDE 4B inhibitors possessing cytotoxic properties against cancer cells.

The 2,2,4-trimethyl-1,2-dihydroquinolinyl substituted 1,2,3-triazole derivatives were designed as potential inhibitors of PDE4B. These compounds were synthesized via a multi-step sequence consisting of copper-catalyzed azide-alkyne cycloaddition (CuAAC) as a key step in aqueous media. The required alkynes were prepared from nimesulide via N-propargylation and then nitro group reduction followed by a CAN mediated modified Skraup reaction of the resulting amine.

A novel no-carrier-added submicromolar scale radiosynthesis of [S-methyl-14C]-florfenicol.

In this paper is reported a novel reaction scheme for the no-carrier-added submicromolar scale radiosynthesis of [S-methyl-(14)C]-florfenicol that has been newly designed, developed and employed by us successfully. The [(14)C]-product was obtained in an overall radiochemical yield of 30% based on [(14)C]-methyl iodide taken for the reaction with a radiochemical purity of more than 96%. The specific activity of the product was ~50 mCi (1.

A facile synthesis of deuterium labeled 2,2-dimethyl-[2H6]-succinic acid and its anhydride.

Deuterium labeled 2,2-dimethyl-[(2)H(6)]-succinic anhydride by a sequence of reactions involving Knoevenagel condensation of [(2)H(6)]-acetone with ethyl cyanoacetate in the presence of piperidine, Michael addition of cyanide, HCl hydrolysis, simultaneous decarboxylation, and subsequent dehydration using acetic anhydride in an overall yield of 34.23% based on [(2)H(6)]-acetone utilized in the reaction is reported. The title compounds were characterized and confirmed spectroscopically by Fourier transform infrared, (1) H-NMR, and Mass.

Ligand/PTC-free intramolecular Heck reaction: synthesis of pyrroloquinoxalines and their evaluation against PDE4/luciferase/oral cancer cell growth in vitro and zebrafish in vivo.

A series of 1,3-disubstituted pyrrolo[2,3-b]quinoxalines has been designed for the potential inhibition of PDE4 without inhibiting luciferase. A ligand/PTC (phase transfer catalyst) free intramolecular Heck cyclization strategy was used to prepare these compounds, some of which showed significant inhibition of PDE4B (IC50≈ 5-14 μM) and growth inhibition of oral cancer cells (CAL 27) but not inhibition of luciferase in vitro. They also showed acceptable safety profiles but no apoptosis in zebrafish embryos.

RP-UPLC method development and validation for the simultaneous estimation of ibuprofen and famotidine in pharmaceutical dosage form.

Aim And Background: A stability-indicating LC method was developed for the simultaneous determination of Ibuprofen and Famotidine in pharmaceutical dosage forms.

Materials And Methods: The chromatographic separation was achieved on Acquity UPLC BEH C-18,50 mm × 2.1 mm and 1.

Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors.

A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via the design and Pd/C mediated synthesis of novel N-indolylmethyl olanzapine derivatives. One compound showed good inhibition (IC50 1.1 μM) and >10 fold selectivity towards PDE4B over D that was supported by docking studies.

Simultaneous quantitation of IC87114, roflumilast and its active metabolite roflumilast N-oxide in plasma by LC-MS/MS: application for a pharmacokinetic study.

A sensitive and reliable high-performance liquid chromatography-mass spectrometry (LC-MS/MS) was developed and validated for simultaneous quantification IC87114, roflumilast (RFM), and its active metabolite roflumilast N-oxide (RFN) using tolbutamide as an internal standard. The analytes were extracted by using liquid-liquid extraction and separated on a reverse phase C(18) column (50 mm × 3 mm i.d.

A convenient photosynthesis of uniformly [¹⁴C]-labelled D-glucose, D-fructose and sucrose, and chemical synthesis of methyl-α-D-glucopyranoside ([U-¹⁴C]-glucose).

This paper describes a convenient procedure for the radiochemical preparation of d-[U-(14)C]-glucose, d-[U-(14)C]-fructose and [U-(14)C]-sucrose with high specific activity by photosynthesis using 'canna indica' leaf, [(14)C]-carbon dioxide and water in presence of light in a closed system. The [(14)C]-sugars formed were extracted, separated and then purified by paper chromatography. Further, the pure d-[U-(14)C]-glucose obtained was converted to methyl-α-d-glucopyranoside ([U-(14)C]-glucose) by glycosidation with methanol using (i) HCl, the conventional Fischer method (ii) heterogeneous organic cation exchange resin (Amberlite IR-120 (H(+))) and (iii) heterogeneous inorganic cation exchanged montmorillonites called metal M(+n)-monts.

A facile no-carrier-added one pot micro-molar scale radiosynthesis of 2-[¹⁴C]-uracil.

A facile no-carrier-added one pot micro-molar scale radiolabelled synthesis of 2-[(14)C]-uracil from [(14)C]-urea and propiolic acid in the presence of polyphosphoric acid (PPA) with an yield of 48.33% and with radiochemical purity of 98% is reported in this paper.

Development and validation of RP-UPLC method for the determination of darifenacin hydrobromide, its related compounds and its degradation products using design of experiments.

A selective stability-indicating ultra-performance liquid chromatographic (UPLC) method was developed for the quantitative determination of darifenacin hydrobromide (DFN) and its related compounds in API and pharmaceutical dosages. The chromatographic separation was achieved on an Acquity UPLC BEH C18 column (100, 2.1 mm and 1.

A novel reverse phase stability indicating RP-UPLC method for the quantitative determination of fifteen related substances in Ranolazine drug substance and drug product.

A gradient reverse-phase ultra performance liquid chromatographic (RP-UPLC) method was developed for the quantitative determination of Ranolazine and potential process-related impurities (starting materials, positional isomers, degradants and byproducts) at the level of 0.1 μg mL(-1) to 0.3 μg mL(-1).

Synthesis and cytotoxicity testing of new amido-substituted triazolopyrrolo[2,1-c][1,4]benzodiazepine (PBDT) derivatives.

A series of amido-substituted triazolopyrrolo[2,1-c][1,4]benzodiazepine (PBDT) derivatives was synthesized from isatoic anhydride, and their cytotoxicity against the MRC-5 and Mahlavu cell lines was evaluated. The results suggest that compound PBDT-7i with the meta-trifluoromethylbenzoyl substituent can selectively inhibit the growth of Mahlavu cells and has low toxicity towards MRC-5 cells.

Liquid chromatography - tandem mass spectrometry for the simultaneous quantitation of glipizide, cilostazol and its active metabolite 3, 4-dehydro-cilostazol in rat plasma: application for a pharmacokinetic study.

A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the simultaneous quantitation of glipizide, cilostazol and 3, 4-dehydro-cilostazol in rat plasma was developed and validated. Glimepride was used as an internal standard (IS). The analytes were extracted by using liquid-liquid extraction procedure and separated on a reverse phase C18 column (50 mm×4.

Development and validation of an LC-ESI-MS method for quantitative determination of aripiprazole in human plasma and an application to pharmacokinetic study.

A selective, sensitive, high pressure liquid chromatography-positive electrospray ionization tandem mass spectrometry method was developed and validated for the quantification of aripiprazole in human K(2)EDTA plasma using zolpidem tartrate as an internal standard. The analyte and internal standard were extracted from human plasma by solid-phase extraction using methanol. The eluted samples were chromatographed on a Grace Smart RP 18 4.

Pharmacokinetic profiling of efavirenz-emtricitabine-tenofovir fixed dose combination in pregnant and non-pregnant rats.

During pregnancy, the disposition of various drugs is altered due to changes in physiological condition, maternal gastrointestinal absorption, gastric secretion and motility. A fixed dose combination of antiretrovirals is commonly prescribed for the treatment of HIV infection. There is a need to understand the pharmacokinetics and placental transfer of efavirenz-emtricitabine-tenofovir in fixed dose combination during pregnancy.

Solvent effect on copper-catalyzed azide-alkyne cycloaddition (CuAAC): synthesis of novel triazolyl substituted quinolines as potential anticancer agents.

A regioselective route to novel mono triazolyl substituted quinolines has been developed via copper-catalyzed azide-alkyne cycloaddition (CuAAC) of 2,4-diazidoquinoline with terminal alkynes in DMF. The reaction provided bis triazolyl substituted quinolines when performed in water in the presence of Et(3)N. A number of the compounds synthesized showed promising anti-proliferative properties when tested in vitro especially against breast cancer cells.

Stability-indicating UPLC method for determination of Imatinib Mesylate and their degradation products in active pharmaceutical ingredient and pharmaceutical dosage forms.

A simple, precise, accurate stability-indicating gradient reverse phase ultra-performance liquid chromatographic (RP-UPLC) method was developed for quantitative determination of purity of Imatinib Mesylate (IMM) drug substance and drug products in the presence of its process related impurities, and degradation products. The proposed RP-UPLC method utilizes Acquity UPLC BEH 50-mm, 2.1mm and 1.

Simultaneous Determination of Sitagliptin Phosphate Monohydrate and Metformin Hydrochloride in Tablets by a Validated UPLC Method.

A novel approach was used to develop and validate a rapid, specific, accurate and precise reverse phase ultra performance liquid chromatographic (UPLC) method for the simultaneous determination of Sitagliptin phosphate monohydrate and Metformin hydrochloride in pharmaceutical dosage forms. The chromatographic separation was achieved on Aquity UPLC BEH C8 100 × 2.1 mm, 1.

Design and synthesis of 4-alkynyl pyrazoles as inhibitors of PDE4: a practical access via Pd/C-Cu catalysis.

The design and synthesis of 4-alkynyl pyrazole derivatives has led to the identification of new class of PDE4 inhibitors. All these compounds were accessed for the first time via a facile Pd/C-CuI-PPh(3) mediated C-C bond forming reaction between an appropriate pyrazole iodide and various terminal alkynes. In vitro PDE4B inhibitory properties and molecular modeling studies of some of the compounds synthesized indicated that 4-alkynyl pyrazole could be a promising template for the discovery of novel PDE4 inhibitors.