The synthesis, X-ray crystal structures, and photochemical behavior of a series of methyl- and ethylene-bridge-substituted trans-4-(N-(4-cyanophenyl)amino)stilbenes (3-8) are reported and compared to those of the parent compound 1CN. Aminostilbene 1CN displays dual fluorescence in polar solvents due to planar and twisted intramolecular charge-transfer (PICT and TICT) states. Alkyl substitution on the stilbene group of 1CN significantly perturbs its photochemistry, including fluorescence, trans --> cis photoisomerization, and TICT state formation. The alkyl substituent effect can be dissected into electronic and steric influences, and both are position dependent, which is vinyl alpha-carbon > vinyl beta-carbon > phenyl o-carbon. The main outcome of the alkyl substituent effect is to lower the barrier for the singlet-state photoisomerization. As a result, the quantum yield for photoisomerization is increased, and that for fluorescence is reduced. The corresponding quantum yield for TICT state formation in polar solvents is reduced only when significant ground-state twisting (a steric influence) is present. The alkyl substitution exerts little or no effect on the rate of intersystem crossing.

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Electrochemical behavior of a biologically active pyridinylpyrimidine derivative, 1-(3-hydroxy-2-pyridyl)-4,4,6-trimethyl-3,4-dihydropyrimidine-2[1H]-thione (1) has been investigated in aqueous phosphate buffers (1.9–10.6) at a pyrolytic graphite electrode (PGE). The oxidation occurred in a single well-defined oxidation peak, Ia, in the pH range 1.9–10.6. In the pH range 4.9–10.6, a reduction peak, IIc, was noticed in the reverse sweep that formed a quasi-reversible couple with peak IIa observed in the subsequent sweep towards positive potentials. The effect of concentration and sweep rate on peak potential and peak current of peak Ia established adsorption of 1 at the surface of PGE. Controlled potential coulometry experiments revealed the 5e− oxidation of 1 in acidic solution and 7e− oxidation in a neutral solution by an EC mechanism. UV–vis spectral and kinetic studies suggested formation of different intermediates in acidic and neutral media. The major product of oxidation at pH 2.7 was characterized as 2,2,4-trimethyl-2H-9-oxa-10-thia-1,4a,5-triazaphenanthrene 10,10-dioxide (6). At physiological pH 7.1, 1-(2,5-dioxo-6-pyridyl)-4,4,6-trimethyl-1,4-dihydropyrimidine-2-thiol (7a) and 1-(3,6-dioxo-3,6-dihydro-2-pyridyl)-4,4,6-trimethyl-1,4-dihydropyrimidine-2-sulfonic acid (10) were identified as the oxidation products by GC-MS. A mechanism for the electrooxidation of 1 at PGE has also been suggested.

Non steroidal anti-in®ammatory drugs are the most widely used medicines for relief of pain. These drugs have some side e¬ects, particularly toxicity in the gastrointestinal tract and kidneys. Various approaches have been used for obtaining safer anti-in®ammatory drugs. In this review we have summarized the recent developments in the following areas; (i) Mode of action of NSAIDs, (ii) Role of COX-1 & COX-2 in in®ammation, (iii) Di¬erent approaches used to improve gastric tolerance i.e chemical manipulation, formulation & co-administration, development of non speci c (COX

Alcaftadine is an active pharmaceutical ingredient (API) used as an ophthalmic solution for the prevention of itching associated with allergic conjunctivitis. The originally reported synthesis uses a time-consuming column chromatography technique for the isolation of hydroxymethylated product alcohol (10). A simple yet effective double oxidation strategy is developed using oxidation grade manganese dioxide to avoid tedious chromatographic purification. Firstly, a partial oxidation of hydroxymethylated crude mass (mixture of compounds 9, 10 and 16) was carried out using a limited amount of MnO2 to get rid of critical diol impurity (16) and to allow crystallization of alcohol (10) crude, followed by its second oxidation using additional MnO2 to provide alcaftadine via a scale-up friendly process. This synthetic approach has been proven to be cost effective and commercially viable. Various impurities formed during the process were also identified and eliminated to obtain ICH guideline purity of alcaftadine API. The process was validated in plant scale and US DMF was filed to manufacture alcaftadine API.

Enantioselective Synthesis of Phenyl-ethanolamines Through Application of Chiral Sulfoxide. -The presented synthetic approach is extended to the asymmetric synthesis of (R)-salbutamol via deprotection of compound (VIIb) (some yields not given).-(SIVAKUMAR, A. V.; LAHOTI, A. M.; BHAT*, S. V.; Synth.