Abstract: This article describes the biosynthesis and identification of a new class of metabolites, a piperazine N-oxide/N-glucuronide metabolite 4-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-1-β-D-glucuronic acid-piperazine 1-oxide (4). The metabolite was found in urine and plasma from humans and animals dosed with 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine hydrobromide (Lu AA21004, 1), as a novel multimodal antidepressant under development for treatment of depression. Human liver microsomes in combination with uridine 5'-diphosphoglucuronic acid were used as an in vitro system to generate enough material of 4 to perform one- and two-dimensional (1)H and (13)C NMR experiments for structure elucidation. Based on rotating frame Overhauser enhancement spectroscopy NMR experiments, the distance correlation between a piperazine proton and the anomeric proton of the glucuronic acid moiety is of a magnitude similar to that of the H-3' and H-5' protons and can only be explained by proximity in space and the postulated structure (4). The structural analog, the N-O-glucuronic acid conjugate 6-{4-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazin-1-yloxy}-1-β-D-glucuronic acid (3) was also observed in biological samples from humans and animals and the first organic synthesis and structural identification of this metabolite is also reported. Treatment of the glucuronide metabolites 3 and 4 with β-glucuronidase gave mainly the expected hydrolysis product, the hydroxyl amine 4-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazin-1-ol (2).

Abstract: New carbamoylpyridine and carbamoylpiperidine analogues containing nipecotic acid scaffold were designed, synthesized, and evaluated for their platelet aggregation inhibitory activity. Molecular modeling investigation was performed and the impact of lipophilicity on activity was also discussed. Structure activity relationship among this series was obtained. N 1-[1-(4-bromobenzyl)-3-piperidino-carbonyl]-N 4-(2-chlorophenyl)-piperazine hydrobromide (20), and 1,4-bis-[3-[N 4-(2-chlorophenyl)-N 1-(piperazino-carbonyl)]-piperidin-1-yl-methyl]-benzene dibromide (30) are the most active antiplatelet aggregating compounds in this study, both at concentration of 0.06 μM.

Abstract: Provided herein are novel solid state forms of etoricoxib salts, process for their preparation, pharmaceutical compositions, and method of treating thereof. The etoricoxib salts include an oxalate salt, a succinate salt, a fumarate salt, a besylate salt, a hydrobromide salt, a glutamate salt, a sulfamate salt, a benzoate salt, a cinnamate salt, a salicylate salt, or a tosylate salt. The solid state forms of etoricoxib salts disclosed herein are useful for preparing etoricoxib free base with high purity.

Abstract: A simple, accurate and specific UV spectrophotometric method was developed and validated for the estimation of Darifenacin hydrobromide in bulk and tablet dosage form. Analyte showed the absorption maxima in 0.1M Hydrochloric acid at 284nm. The percentage recovery of Darifenacin Hydrobromide was 99.69±0.14%. The developed method was validated with respect to linearity, accuracy, precision and specificity. Beer's law was obeyed in the concentration range of 20.00μg/mL to 46.50μg/mL, having line equation y=0.059x+0.0177 with correlation coefficient of 0.999. Results of the analysis were validated statistically as per ICH guidelines.

Abstract: The present invention provides a salt of Tapentadol, Tapentadol liydrobromide, and crystalline forms of Tapentadol hydrobromide.

Abstract: SEVERAL methods for the determination of hyoscine hydrobromide in pharmaceutical preparations have been described in the l i terat~re.l?~*~ In general, however, these methods are not suitable for the determination of very low proportions of the alkaloid, particularly in the presence of interfering substances, and the object of the work described here was to devise a method capable of determining amounts of hyoscine hydrobromide of the order of 0.005 per cent. w/v of solution. Kirkpatrick4 has studied the catalytic reduction of a number of alkaloids, including hyoscine at the dropping mercury electrode. A method based on this principle has been found to give quantitative results when applied to solutions of hyoscine hydrobromide but the presence of electrolytes (other than those specified for the base solution) and of traces of other alkaloids renders the method unsuitable for routine application. Allport and Wilson6 have studied Morin’s6 modification of Vitali‘s test for solanaceous alkaloids and have applied it successfully to belladonna, stramonium and their galenical preparations, whilst Allport and Jones7 have extended the application of this reaction to the determination of atropine, hyoscyamine and hyoscine in hypodermic tablets and injection solutions. Other workers* have reported that this method gives accurate and reproducible results only when the reagents, the reaction times and the water content of the acetone are rigidly controlled. Preliminary experiments in these laboratories on hyoscine hydrobromide solutions have confirmed these findings. Attention was, therefore, directed to investigating the factors affecting Allport and Wilson’s method and to applying the method to the determination of hyoscine hydrobromide (a) in official preparations and (b) in solutions of pethidine hydrochloride containing hyoscine : such solutions are commercially available as injection preparations containing usually 0.0108 per cent. w/v or 0-0216 per cent. w/v hyoscine hydrobromide in a 5.0 per cent. w/v solution of pethidine hydrochloride containing a preservative. The sample of hyoscine hydrobromide used throughout the investigation conformed to the requirements of the British Pharmacopceia 1948 and except where otherwise stated other reagents were of “Analar” quality.

Abstract: Possibility of obtaining water-soluble N- and N,N′-coordinated adducts by reacting 3,7-dithia-1,5-diazabicyclo[3.3.0]octane with methyl iodide and Bronsted (HCl, HBr) and Lewis (AlCl3) acids was examined. The fungicidal activity of 3,7-dithia-1,5-diazabicyclo[3.3.0]octane and its water-soluble adducts with hydrobromide and methyl iodide against a number of microscopic fungi affecting cultivated plants and various materials was studied.

Abstract: An agomelatine hydrobromide hydrate of formula (I), in which X is Br, preparation method and use thereof as well as pharmaceutical composition containing it are provided. The solubility of the agomelatine hydrobromide hydrate obtained by the present method is significantly higher than that of agomelatine. Therefore, it is more suitable for manufacturing pharmaceutical formulations. In addition, the product has higher stability and purity. The present product of high purity can be obtained through a simple process, rather than process with complicated steps.

Abstract: An efficient oxidative esterification of aromatic and aliphatic aldehydes with simple alcohols was accomplished using catalytic amounts of 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU) hydrobromide-per...

Abstract: [Problem] A salt or crystal of a compound which is highly stable in a solid state and useful as a bulk material for the preparation of a pharmaceutical product is provided. [Means for Solution] 4-{[(1R,2s,3S,5s,7s)-5-Hydroxy-2-adamantyl]amino}-1H-pyrrolo[2,3-b]pyridine-5-carboxamide succinate, 4-{[(1R,2s,3S,5s,7s)-5-hydroxy-2-adamantyl]amino}-1H-pyrrolo[2,3-b]pyridine-5-carboxamide hydrobromide, and 4-{[(1R,2s,3S,5s,7s)-5-hydroxy-2-adamantyl]amino}-1H-pyrrolo[2,3-b]pyridine-5-carboxamide hydrochloride and crystals thereof are useful as a bulk material for the preparation of a solid preparation, in particular, a solid dispersion preparation. Furthermore, the crystal of the hydrobromide has excellent stability in a solid state and is useful as a bulk material for the preparation of a pharmaceutical product.

Abstract: The use of the anorexigenic drug aminorex has been associated with a high incidence of progressive pulmonary hypertension (Gurtner, Gertsch & others, 1968), so too has chlorphentermine (Rau, 1969; Paeprer, 1970). As a result, anorexigenic drugs are suspected of causing pulmonary hypertension. We have compared the effects of the repeated acute administration of the anorexigenic agents DITA (3',4'-dichloro-2-(2-imidazolin-2-yl-thio)-acetophenone hydrobromide, Abdallah & White, 1974) and diethylpropion on the systemic and pulmonary arterial blood pressure of anaesthetized dogs. Mongrel dogs of either sex, 7 to 24 kg, were anaesthetized with pentobarbitone sodium (32.5 mg kg-', i.p.). Pulmonary arterial blood pressure was recorded by catheterization of either the femoral or jugular vein. The position of the tip of the catheter was verified by monitoring the changes in blood pressure as the catheter was advanced. The system was filled with a 0.9 % solution of sodium chloride (saline) which contained 10 units ml-' of heparin. Systemic arterial pressure was measured from a femoral artery cannulated with plastic tubing and attached to a pressure transducer. Mean pulmonary and systemic arterial blood pressures were recorded directly. Dogs were heparinized with 500 units kg-l (i.v.). A femoral vein was cannulated for the administration of drugs which were dissolved in saline shortly before use. (No change in blood pressure was observed on injection of vehicle alone). Each dog received one dose (2,4 or 8 mg kg-l) of the anorexigenic compound every 30min for 5 doses and 3 dogs were

Abstract: The present invention relates to an improved process for the preparation of 3-(N-methyl-2(R)-pyrrolidinyl methyl)-5-[2-(phenyl sulfonyl)ethyl]-1H-indole or pharmaceutically acceptable salts thereof, particularly 3-(N-methyl-2(R)-pyrrolidinyl methyl)-5-[2-(phenyl sulfonyl)ethyl]-1H-indole hydrobromide (Eletriptan hydrobromide). The present invention further relates to novel polymorphs of 3-(N-methyl-2(R)-pyrrolidinyl methyl)-5-[2-(phenyl sulfonyl)ethenyl]-1H-indole hydrobromide and process for preparation thereof.

Abstract: FIELD: medicine, pharmaceutics. ^ SUBSTANCE: invention relates to field of pharmacology and medicine and deals with application of 2-morpholino-5-phenyl-6H-1,3,4-tiazin hydrobromide as medication, possessing hypolipidemic and hyperglycemic action. ^ EFFECT: obtaining medication, possessing hypolipidemic and hyperglycemic action. ^ 8 dwg, 1 tbl

Abstract: Provided herein are hydrobromide salts of a pyrazolylaminoquinazoline, and pharmaceutical compositions thereof. Also provided are methods of their use for treating, preventing, or ameliorating a proliferative disease.

Abstract: A polymorphous form of the hydrobromide of prasugrel, a well-known substance reducing blood coagulation, prasugrel of formula (I), which is characterized by high chemical stability, and a method for its production. (Formula (I))

Abstract: Crystalline forms of Nilotinib hydrobromide, succinate, glutamate, acetate, L-malate and maleate acid addition salts, polymorphs thereof and a process for the preparation of Nilotinib hydrochloride and Nilotinib base from any one of these salts

Abstract: An agomelatine hydrobromide hydrate of formula (I), in which X is Br, preparation method and use thereof as well as pharmaceutical composition containing it are provided. The solubility of the agomelatine hydrobromide hydrate obtained by the present method is significantly higher than that of agomelatine. Therefore, it is more suitable for manufacturing pharmaceutical formulations. In addition, the product has higher stability and purity. The present product of high purity can be obtained through a simple process, rather than process with complicated steps.

Abstract: Reaction of 1-methylpyrimidine-(1H,3H,5H)-2,4,6-trione (1-MBA 1) as an unsymmetrical barbituric acid with cyanogen bromide and various aldehydes in the presence of triethylamine and/or pyridine afforded diastereomeric mixtures of new class of heterocyclic stable 5-aryl-1,1'-dimethyl- and 5-aryl-3,1'-dimethyl-1H,1'H-spiro(furo(2,3-d)pyrimidine-6,5'- pyrimidine)2,2',4,4',6'(3H,3'H,5H)-pentaones which are dimeric forms of 1-methyl barbiturate at the range of 0 o C to room temperature. In the reaction of some aldehydes with 1-MBA and BrCN were afforded a mixture of diastereomers. Another two aldehydes such as 4-cyano- and 2-hydroxybenzaldehydes gave exclusively two diastereomers in which binded to the salt of triethylammonium hydrobromide by intermolecular H-bond in ratio of 1:1. 4-Hydroxybenzaldehyde and 2-pyridine- carbaldehyde gave exclusively one diastereomer under the same condition. Aldehydes possessing strong electron-donor were produced exclusively two geometric isomers of Knoevenagel adduct (E- and Z-isomers). The structures of compounds were deduced by 1 H NMR, 13 C NMR and FT-IR spectroscopy. Mechanism of the formation is discussed.