Stable Fatty Acid Solvates of Dasatinib, a Tyrosine Kinase Inhibitor: Prediction, Process, and Physicochemical Properties.

Exploration of alternate solid forms for dasatinib, a potent oncogene tyrosine kinase inhibitor classified under Biopharmaceutics Classification System (BCS) class II drugs with low water solubility and high permeability, has been performed using COSMO-RS excess enthalpy (Hex) to increase dissolution. The theoretical prediction resulted in the potential for the formation of C-C fatty acid solvates with dasatinib. A crystallization process has been identified for the preparation of the predicted solvates and successfully scaled up till the 100 g level.

Facile Synthesis of Dabigatran Etexilate Mesylate, an Anticoagulant Drug, Using a Novel Synthon, -Hexyl-4-nitrophenyl Carbonate.

Facile synthesis for Dabigatran etexilate mesylate (), an anticoagulant drug, is reported using a novel synthon, -hexyl-4-nitrophenyl carbonate (), which substantially eliminates the formation of potential impurities -, which were generated due to the use of -hexyl chloroformate in previously reported methods. Pinner reaction to prepare a key and critical intermediate, amidine , was optimized using design of experiment software to establish critical process parameters to achieve in 97% yield. Nucleophilic substitution of with novel synthon -hexyl-4-nitrophenyl carbonate () furnished the dabigatran base , which was then converted to its mesylate salt using methane sulfonic acid to provide with an overall yield of 66% over three steps.

Investigation of Mechanistic Pathway for Trimethyl Borate Mediated Amidation of (R)-Mandelic Acid for the Synthesis of Mirabegron, an Antimuscarinic Agent.

The present work describes investigation of mechanistic pathway for trimethyl borate mediated amidation of (R)-mandelic acid (3) with 4-nitophenylethylamine (2) to provide (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide (4) during mirabegron synthesis. Plausible reaction mechanism is proposed by isolating and elucidating the active α-hydroxy ester intermediate 16 from the reaction mass. Trimethyl borate mediated approach proved to be selective in providing 4 without disturbing α-hydroxyl group and stereochemistry of the chiral center, and is also a greener, more economic and production friendly over the reported methods.

An efficient and safe process for the preparation of ticagrelor, a platelet aggregation inhibitor via resin-NO2 catalyzed formation of triazole ring.

An efficient, safe and improved process for the preparation of ticagrelor 1, a platelet aggregation inhibitor is described. Synthesis comprises the condensation of pyrimidine amine derivative 14 with cyclopentyl derivative 13 in ethylene glycol followed by construction of triazole compound 16 by diazotization of the obtained intermediate 15 with a green and safer reagent "Resin-NO2" in water and acetonitrile mixture. Condensation of 16 with cyclopropylamine derivative 10 followed by deprotection of compound 12 with hydrochloric acid in dichloromethane (DCM) furnished ticagrelor 1 with an overall yield of 65 % and purity of 99.

Synthesis and fluorescence properties of donor-acceptor-substituted novel dipyrazolo[3,4-b:3',4'-d]pyridines (DPP).

A rapid and efficient method for the synthesis of novel dipyrazolo[3,4-b:3',4'-d]pyridines (DPP) from pyrazolo[3,4-b]pyridine was successfully developed. The DPP derivative was further N-alkylated (6, 8) as well as N-linked with amino acids (13) and their photophysical properties were studied along with N-aryl DPP 4 and observed that the chromophores at C(4) position in the aryl ring changed the absorption and emission lambda(max).

Shikonin analogue (SA) 93/637 induces apoptosis by activation of caspase-3 in U937 cells.

Beta,beta-dimethyl acryl shikonin is an extract from the root of plant Arnebia nobilis which has been shown to possess anti-cancer activity. However, its toxicity limited further development of shikonin as a therapeutic agent. Subsequently, several analogues of beta,beta-dimethyl acryl shikonin were synthesized.

A novel quantification method of pantaprazole sodium monohydrate in sesquihydrate by thermogravimetric analyzer.

To demonstrate the applicability of thermogravimetric analyzer as a tool for the quantification of pantaprazole sodium monohydrate in sesquihydrate, studies have been conducted. Thermal analysis (DSC, TGA) crystallographic (PXRD) and spectroscopic techniques (FT-IR) were used for the characterization of the polymorphs. Thermogravimetric analysis (TGA) analysis was explored by high-resolution dynamic (Hi-Res-dynamic) and high-resolution modulated (Hi-Res-modulated) test procedures to quantify the hydrate polymorphic mixtures.

Oxidation studies on Andrographolide.

Jones oxidation of Andrographolide (1), gave mixture of three products (3-dehydroandrographolide (5), 3,19-bis dehydroandrographolide (6) and 19-dehydroandrographolide (7). Tritylation of andrographolide at C19-OH resulted to products 8 and diene 9, which can be converted to its acetate 10 and oxidation product 11.

Identification and characterization of potential impurities of donepezil.

Five unknown impurities ranging from 0.05 to 0.2% in donepezil were detected by a simple isocratic reversed-phase high performance liquid chromatography (HPLC).

Impurity profile study of repaglinide.

Three unknown impurities and a byproduct in repaglinide bulk drug at levels below 0.1% (ranging from 0.05 to 0.