Therapeutic formulations and methods for inhibiting amyloid deposition in a subject, whatever its clinical setting, are described. Therapeutic formulations and methods for preventing or treating amyloidosis and/or amyloid-related disease are also described.

Pharmaceutical formulations of amyloid inhibiting compounds

Bisphenol-A is prepared by reacting an excess of phenol with acetone in the presence of a modified sulfonic acid cationic exchange resin catalyst having a plurality of sulfonic acid sites of the general formula ##STR1## in which IER represents the ionic exchange resin backbone, each a and b is an integer from 0 to about 5, and each R is selected independently from H, OH, SH and alkyl groups. The catalyst exhibits high activity and selectivity at moderate reaction temperatures, low production of colored impurities, and high stability.

Process and alkylmercaptoamine catalyst for production of bisphenol-A

The invention relates to methods, compounds, compositions and vehicles for delivering 3-amino-1 -propanesulfonic acid (3APS) in a subject, preferably a human subject The invention encompasses compounds that will yield or generate 3APS, either in vitro or in vivo Preferred compounds include amino acid prodrugs of 3APS for use, including but not limited to, the prevention and treatment of Alzheimer's disease

Methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid

Methods, formulations, and compositions for the treatment of amyloidosis are described, whereby a therapeutically effective amount of a compound having the formula (I) wherein Y is SO3X or OSO3X independently chosen for each occurrence; X is cationic group independently chosen for each occurrence; n is 1, 2, 3 or 4; and m is 1 or 2, is applied.

Formulations and methods for treating amyloidosis

Disclosed herein are methods, compounds and compositions for preventing or treating a renal disorder or chronic kidney diseases, including nephropathies such as diabetic nephropathy. The invention generally includes administering to a subject 1,3-propanedisulfonic acid or a pharmaceutically acceptable salt thereof, e.g., 1,3- propanedisulfonic acid sodium salt. The invention also relates to methods, compounds and compositions for the prevention and/or treatment of for preventing or treating a renal disorder complication. The invention further relates to methods, compounds and compositions for the prevention and/or treatment of dyslipidemia, and more particularly for reducing levels of harmful serum lipid levels, especially cholesterol and triglycerides in diabetic patients.

Treatment of renal disorders, diabetic nephropathy and dyslipidemias

Disclosed herein is a process for preparing with a high yield an aminoalkylsulfonic acid represented by the following general formula: ##STR1## wherein R1, R2 and R3 are each a hydrogen atom, an alkyl group having 1-3 carbon atoms or a hydroxyl-containing alkyl group having 1-3 carbon atoms and n stands for an integer of 2 or 3, which process comprises reacting a sulfite with a halogenated alkylamine represented by the following general formula: ##STR2## wherein X means a chlorine, bromine or iodine atom, and R1, R2, R3 and n have the same meanings as defined above by adding the halogenated alkylamine little by little either continuously or intermittently over a certain period of time to a heated aqueous solution of the sulfite. The yield may be increased further when, after the addition of the halogenated alkylamine, the reaction is carried out by raising the reaction temperature stepwise in 2-5 stages while limiting the reaction time and temperature-raising range in each stage to 0.5-4 hours and 10°-20° C.

Production of aminoalkylsulfonic acids

PURPOSE:To obtain the titled compound useful as a drug, etc. inexpensively in high purity in high yield with sppressing side reactions, by subjecting an aqueous solution containing both a sulfite and a halogenoethylamine to reactions with raising the reaction temperatures stepwise in a specific temperature range. CONSTITUTION:An aqueous solution containing a halogenated alkylamine shown by the formula I (R1-R3 are C, or 1-3C alkyl containing 1-3C alkyl; X is Cl, Br, etc.; n is 2 or 3) and a sulfite (e.g., sodium sulfate, etc.) is subjected to reactions in such a way that at least one or more time constant temperature reactions are carried out in a temperature range of normal temperature -65 deg.C and in a temperature range of 50 deg.C- the reflux temperature of the aqueous solution, respectively, and the temperatures are raised at least two times, to give an aminoalkylsulfonic acid shown by the formula II. The reactions suppress side reactions such as hydrolysis, etc., and result in suppression of by-products. The raw material compounds are extremely safe, easily treatable and inexpensive.

Preparation of aminoalkylsulfonic acids

PURPOSE:To shorten the reaction time, and to improve the purity of the product in the preparation of an aminoalkylthiol useful as a raw material of pharmaceuticals by the hydrolysis of 2-mercaptothiazoline compound, by terminating the reaction at a specific range of conversion. CONSTITUTION:The objective compound of formula II (R , R , R and R are H, lower alkyl or hydroxy-substituted lower alkyl) is prepared in high purity, by hydrolyzing a 2-mercaptothiazoline compound of formulaIwith a hydrohalogenic acid (HX), terminating the reaction when the conversion reaches 80-95%, and recrystallizing the resultant crude aminoalkylthiol with an organic solvent. The hydrohalogenic acid is e.g. hydrofluoric acid, hydrochloric acid, etc., and its amount is 4-8mol per 1mol of the 2-mercaptothiazoline compound. EFFECT:The hydrolytic conversion of as high as 80-95% can be attained easily by suppressing the successive reaction through intermediates and carrying out the direct reaction preferentially.

Preparation of aminoalkylthiol

A process for producing in a high yield aminoalkylsulfonic acids represented by the formula (I) wherein R1, R2, and R3 each represent hydrogen, C1-3 alkyl or hydroxy-containing C1-3 alkyl, X represents chlorine, bromine or iodine and n represents 2 or 3, which process comprises adding continuously or intermittently by portions over a certain period of time to a heated aqueous sulfite solution a alkylamine hydrohalide represented by the formula (II). The yield can be increased by conducting the reaction, after the addition of the alkylamine hydrohalide, in such a manner that the reaction temperature is stepwise raised in 2 to 5 steps in each of which the reaction time and the temperature-raising rate are set to 0.5 to 4 hours and 10 to 20oC/step, respectively.

Process for producing aminoalkylsulfonic acids

PURPOSE:As a mixture of a halogenated alkylamine and carbon disulfide is kept at a constant low temperature, an alkali hydroxide is added dropwise, then the temperature is raised to effect the reaction, thus the titled compound used as an intermediate of drugs is produced in high purity with inhibition of side- reactions in high yield. CONSTITUTION:A halogenated alkylamine hydrohalide acid salt of formulaI (R1-R4 are H, lower alkyl; X, Y are halogen) and an equimolar or slightly excessive amount of carbon disulfide are mixed and an aqueous solution of alkali hydroxide is added to the mixture dropwise at such a rate as the mixture is kept at a temperature lower than 20 deg.C, preferably lower than 10 deg.C. Usually, the dropping time ranges from 30min to 3hr. After completion of dropping, the reaction is effected at 40-80 deg.C to give the objective compound of formula II. Since a water-soluble surface active agent exists in the reaction mixture, the dispersibility or emulsifiability of carbon disulfide is increased to raise its contact efficiency and its reaction efficiency.

Iwasaki Kouzou

Papers

Production of aminoalkylsulfonic acids

Preparation of aminoalkylsulfonic acids

Preparation of aminoalkylthiol

Process for producing aminoalkylsulfonic acids

Production of 2-mercapto-2-thiazoline