Abstract: Compounds of Formula I are antagonists of VLA-4 and/or &agr;4&bgr;7, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of AIDS-related dementia, allergic conjunctivitis, allergic rhinitis, Alzheimer's disease, asthma, atherosclerosis, autologous bone marrow transplantation, certain types of toxic and immune-based nephritis, contact dermal hypersensitivity, inflammatory bowel disease including ulcerative colitis and Crohn's disease, inflammatory lung diseases, inflammatory sequelae of viral infections, meningitis, multiple sclerosis, multiple myeloma, myocarditis, organ transplantation, psoriasis, pulmonary fibrosis, restenosis, retinitis, rheumatoid arthritis, septic arthritis, stroke, tumor metastasis, uveititis, and type I diabetes.

Abstract: Malonic esters of the general formula where R is C1-10-alkyl, C3-10-alkenyl or aryl-C1-4-alkyl, are prepared by reacting an alkali metal salt of malonic acid with a halide of the general formula R—X (II), where R is as defined above and X is chlorine, bromine or iodine, in the presence of water and a phase-transfer catalyst.

Abstract: There is provided a novel mixed crystal comprising aspartame (APM) and N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine methyl ester, which can be used as a sweetener having considerably improved quality of sweetness, etc. The above mixed crystal can be easily produced industrially by subjecting a solution containing the above-mentioned APM and APM derivative to a crystallizing operation followed by the separation of the mixed crystal thus precipitated.

Abstract: The invention concerns anti-tumour agents of formula (I) wherein each of R1, R2 and R3 has the meanings defined in the specification including hydrogen, (1-4C)alkyl, (3-4)alkenyl, (3-4C)alkynyl, amino, (1-4C)alkylamino and (1-4C)alkoxy; each of R4 and R5 is (1-4C)alkyl; each of R6 and R7 is hydrogen or (1-4C)alkyl; X is oxygen; m is 1 or 2 and each R8 is as defined in the specification; each of Y1 and Y2 is halogeno, (1-4C)alkanesulphonyloxy, benzenesulphonyloxy or phenyl-(1-4C)akanesulphonyloxy; or a pharmaceutically-acceptable salt thereof; provided that at least one of R1, R2 and R3 is other than hydrogen; a process for preparation, pharmaceutical compositions containing them and their use in the production of an anti-proliferative effect.

Abstract: Benzenoid HETE derivatives and methods of their use for treating dry eye are disclosed.

Abstract: There is provided a process for industrially and efficiently producing an optically active N-protected-N-methyl-4-halogenophenylalanine at a high purity, which is useful as an intermediate for the production of pharmaceutical agents. An optically active N-protected-N-methyl-4-halogenophenylalanine (including the free form and/or the salt form thereof) purified to a high purity is produced by way of the deposition and isolation in the form of salt (DCHA salt or the like) from an optically active N-protected-N-methyl-4-halogenophenylalanine containing at least the optical isomer thereof as an impurity. Because the intended compound at a high purity can be recovered and obtained at a high yield, the process of the present invention is very useful as a process for producing the intermediate for the production of pharmaceutical agents.

Abstract: In the separation and purification of N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine methyl ester produced in the reductive alkylation of aspartame (APM) with 3,3-dimethylbutylaldehyde, the APM used in the starting material for the alkylation, which is difficult to be separated by recrystallization only from the crude crystals of the reaction product, can be separated and removed by extraction or solution thereof with the specified organic solvent from the concentrated reaction solution of the reductive alkylation or from the crude crystals of the product therefrom, and further N,N-di(3,3-dimethylbutyl)-APM as the by-product can be separated and removed by means for separation and purification, such as crystallization, chromatography, extraction, treatment with the activated charcoal, etc.

Abstract: A purified N-t-butoxycarbonylphenylalanine ester preparation having an enhanced optical activity can be obtained by bringing an N-t-butoxycarbonylphenylalanine ester preparation containing an optically active compound into contact with an aliphatic hydrocarbon, extracting the optically active compound with the aliphatic hydrocarbon, and recovering the optically active compound from the resulting extract.

Abstract: The present invention relates to a novel process for the preparation of aromatic carbonyl compounds by oxidative cleavage of styrenes using lipases and hydrogen peroxide or hydrogen peroxide donors in the presence of carboxylic acids or carboxylic esters.

Abstract: Heteroatom-interrupted HETE derivatives and methods of their use for treating dry eye are disclosed.

Abstract: Herein is disclosed an aqueous stable lysine solution containing an acid radical in such amount that the solubility of lysine therein has been increased than in the corresponding aqueous lysine base solution, whereby during storage of lysine in the form of a free-lysine solution (liquid composition), the precipitation of lysine base crystals due to the drop in temperature is prevented thereby improving the handling thereof during transportation (transfer) etc.

Abstract: A rapid method for cancer diagnosis which is suitable to detect the presence of a carcinogenic process in a subject in the a symptomatic phase or the early phase. Also disclosed is an activator compound of carbonic anhydrase II, i.e., a tumor marker, which is present in the serum of subjects having cancer, a method of treating cancer, and a kit for performing the method for cancer diagnosis.

Abstract: The present invention relates to a process for producing creatine or creatine-monohydrate, comprising the step of reacting N-methylglycine, sodium N-methylglycinate and/or potassium N-methylglycinate with S-methylisothiourea and/or S-methylisothiourea sulfate in water or in a mixture of water and an alcohol solvent under the temperature from 15° C. to 140° C. and a pH of 7-13. By using the process of the present invention creatine or creatine-monohydrate with a higher purity can be produced at a much lower cost.

Abstract: Disclosed is a method of producing an optically active &bgr;-hydroxy sulfonic acid compound comprising hydrogenating a &bgr;-keto sulfonic acid compound represented by formula 1: where R1 represents an alkyl or a phenyl group, which may be substituted, and R2 represents sodium or an alkyl group, in an acidic solvent, in the presence of an asymmetric catalyst comprising a complex of bivalent Ru, having 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl as a ligand, to produce a compound represented by formula 2: where R1 and R2 are as defined above, and * designates an asymmetric carbon atom.

Abstract: Fluorine-containing amino acid derivatives represented general formula (I), pharmaceutically acceptable salts thereof or hydrates of the same, wherein X1 represents hydrogen or fluorine; and R1 and R2 are the same or different and each represents hydrogen or lower C1-10 alkyl. These compounds are useful as drugs, in particular, group 2 metabotropic glutamate receptor agonists for treating and preventing psychiatric disorders such as schizophrenia, anxiety and associated diseases, depression, bipolar disturbance and epilepsy, and neurological diseases such as drug addiction, cognition disorder, Alzheimer's disease, Huntington's chorea, Parkinson's disease, motility disturbance associating muscular stiffness, cerebral ischemia, cerebral insufficiency, spinal cord lesion and head disturbance.

Abstract: There is provided a process for purification of N-(3,3-dimethylbutyl)-&agr;-L-aspartyl-L-phenylalanine methyl ester comprising the step of contacting impure N-(3,3-dimethylbutyl)-&agr;-L-aspartyl-L-phenylalanine methyl ester containing at least &agr;-L-aspartyl-L-phenylalanine methyl ester as an impurity, with the mixed solvents having two layers of one layer given from at least one organic solvent which does not mix with water homogeneously and one layer of water to extract N-(3,3-dimethylbutyl)-&agr;-L-aspartyl-L-phenylalanine methyl ester in the organic solvent layer. In the present invention, the desired compound can be purified or recovered efficiently in a high yield without using burdensome steps or operations.

Abstract: In accordance with the present invention, there are provided conjugates of a combination of pharmacologically active agents (e.g., NSAIDs and selective COX-2 inhibitors). Invention conjugates provide a new class of pharmacologically active agents (e.g., anti-inflammatory agents) which provide the therapeutic benefits of both NSAIDs and selective COX-2 inhibitors, while causing a much lower incidence of side-effects then are typically observed with such agents due to the protective effects imparted by modifying the pharmacologically active agents as described herein.

Abstract: A method for producing highly purified crystals of tetrasodium. Salt of ethylenediaminetetraacetic acid including reacting ethylene diamine, NaCN and formalin in the presence of an alkali to yield a solution containing EDTA4Na and impurities. This solution is subjected to crystallization over a solvent to form EDTA4Na crystals. The solvent is a mixture of methanol and an alcohol of either ethanol or propanol. The methanol has a ratio by weight to the alcohol of 1:0.43-4.0. The EDTA4Na crystals are then recovered after subjecting the solution to crystallization.

Abstract: The invention provides a method of preparing new crystal forms of aspartame utilizing microemulsions comprising: (a) introducing aspartame into a microemulsion formed from an oil phase, an aqueous phase and at least one emulsifier, (b) destabilizing the microemulsion to effect recrystallization of aspartame; (c) separating solid phase crystals from the liquid phase in which they are contained; and (d) cleaning the crystals to remove traces of the oil phase and surfactant.

Abstract: Carboxylic acids, particularly dicarboxylic acids, are separated from a fermentation broth by adjusting the pH of the fermentation broth to about 2.0 or below, and then heating the broth to a temperature sufficient to cause formation of three immiscible phases, one of which is an organic phase containing the carboxylic acids.