Process of ortho-halogenation of phenylalanine compounds by C—H activation.

The present invention discloses a lithium organic acid-amino acid salt. A lithium organic acid is one or more of lithium isobutyrate, lithium n-butyrate, lithium lactate, lithium citrate or lithium cholesterol; an amino acid is one of L-proline, valine, lysine or artificially synthetic amino acids; and the lithium organic acid-amino acid salt is a salt formed by the lithium organic acid and the amino acid. The present invention further discloses a crystal form, a preparation method and an application of the salt. The lithium organic acid-amino acid salt of the present invention has a positive curative effect and a preventive effect on recurrent episodes of mania and depression in bipolar disorder, and can delay degenerative changes of the central nervous system to realize better distribution in the central nervous system.

The present invention discloses a lithium organic acid-amino acid salt. A lithium organic acid is one or more of lithium isobutyrate, lithium n-butyrate, lithium lactate, lithium citrate or lithium cholesterol; an amino acid is one of L-proline, valine, lysine or artificially synthetic amino acids; and the lithium organic acid-amino acid salt is a salt formed by the lithium organic acid and the amino acid. The present invention further discloses a crystal form, a preparation method and an application of the salt. The lithium organic acid-amino acid salt of the present invention has a positive curative effect and a preventive effect on recurrent episodes of mania and depression in bipolar disorder, and can delay degenerative changes of the central nervous system to realize better distribution in the central nervous system.

The present invention relates to a carbonic acid adduct (CAA) comprising carbonic acid, at least one amine, and optionally at least one salt, said adduct being producible by a method comprising the following steps: a) providing a solution (A) comprising dissolved CO.sub.2; optionally b) dissolving a base (BA) not corresponding to the amine (AM) in the solution (A) so as to obtain the solution (A1); c) dissolving the at least one amine (AM) in the solution (A) or (A1) so as to obtain the solution (B); d) freezing the solution obtained after completion of step c); and e) storing the solution frozen in step d) at −100 to 0° C. for no longer than 4 days. The content of CO.sub.2 in the solution that is subjected to step c) is at least 6 g/l. The invention also relates to a method for producing the carbonic acid adduct (CAA), a pharmaceutical preparation (PP) comprising the carbonic acid adduct (CAA), and methods for the production thereof and use of the carbonic acid adduct (CAA) or the pharmaceutical preparation (PP) in therapy for a range of indications.

The present invention relates to a carbonic acid adduct (CAA) comprising carbonic acid, at least one amine, and optionally at least one salt, said adduct being producible by a method comprising the following steps: a) providing a solution (A) comprising dissolved CO.sub.2; optionally b) dissolving a base (BA) not corresponding to the amine (AM) in the solution (A) so as to obtain the solution (A1); c) dissolving the at least one amine (AM) in the solution (A) or (A1) so as to obtain the solution (B); d) freezing the solution obtained after completion of step c); and e) storing the solution frozen in step d) at −100 to 0° C. for no longer than 4 days. The content of CO.sub.2 in the solution that is subjected to step c) is at least 6 g/l. The invention also relates to a method for producing the carbonic acid adduct (CAA), a pharmaceutical preparation (PP) comprising the carbonic acid adduct (CAA), and methods for the production thereof and use of the carbonic acid adduct (CAA) or the pharmaceutical preparation (PP) in therapy for a range of indications.

The disclosure provides compounds having formula (I):

##STR00001##

and the pharmaceutically acceptable salts thereof, wherein R.sub.1, R.sub.2, R.sub.2′, and X are as defined as set firth in the specification. Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON). The disclosure also provides compounds having formula (I) for use in treating cancer.

The disclosure provides compounds having formula (I):

##STR00001##

and the pharmaceutically acceptable salts thereof, wherein R.sub.1, R.sub.2, R.sub.2′, and X are as defined as set firth in the specification. Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON). The disclosure also provides compounds having formula (I) for use in treating cancer.

Glycine is an organic compound that can be used in the making of a synthetic acid that obviates all the drawbacks of strong acids such as hydrochloric acid. The new compound is made by dissolving glycine in water, in a weight ratio of approximately 1:1 to 1:1.5. The solution is mixed until the glycine is essentially fully dissolved in the water. Once dissolution is complete, hydrogen chloride gas is dissolved in the solution to produce the new compound, which can be referred to as hydrogen glycine. Also disclosed is a method for adjusting the pH of a fluid, the method comprising adding an effective amount of a solution to the fluid for adjusting the pH thereof to a desired level, wherein the solution is prepared by mixing glycine in water to form a glycine solution; and adding hydrogen chloride to the glycine solution.

It is provided a compound of formula (I); wherein R.sup.5 is selected from the group consisting of H, OM, COOM, NH.sub.2, SO.sub.3M, (C.sub.1-C.sub.4)alkyl, and halogen; and A is a radical having at least 3 C atoms selected from the group consisting of: i) a radical of formula (i) wherein R.sup.7 is selected from the group consisting of OM, and COOM, and n is 0, 1 or 2; and ii) a radical of formula (ii) or of formula (iii) wherein R.sup.8 is selected from the group consisting of H, (C.sub.1-C.sub.4)alkyl; and wherein M is independently selected from the group consisting of H, an alkaly metal, and NH.sub.4.sup.+. It is also provided a process for the preparation thereof, a composition comprising it, and its use for correcting deficiencies of metals in plants. ##STR00001##

It is provided a compound of formula (I); wherein R.sup.5 is selected from the group consisting of H, OM, COOM, NH.sub.2, SO.sub.3M, (C.sub.1-C.sub.4)alkyl, and halogen; and A is a radical having at least 3 C atoms selected from the group consisting of: i) a radical of formula (i) wherein R.sup.7 is selected from the group consisting of OM, and COOM, and n is 0, 1 or 2; and ii) a radical of formula (ii) or of formula (iii) wherein R.sup.8 is selected from the group consisting of H, (C.sub.1-C.sub.4)alkyl; and wherein M is independently selected from the group consisting of H, an alkaly metal, and NH.sub.4.sup.+. It is also provided a process for the preparation thereof, a composition comprising it, and its use for correcting deficiencies of metals in plants. ##STR00001##