Allulose crystals are efficiently produced from an allulose syrup using seed crystals.

Allulose crystals are efficiently produced from an allulose syrup using seed crystals.

The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure.

The invention relates to novel camptothecin derivatives and their applications, tumor cell growth inhibitors, ternary complexes, and a method for improving the solubility of the camptothecin derivatives. The camptothecin derivatives are prepared by modifying the substance shown as Formula I with glycosylated triazole at position R.sup.3. In the structure shown as Formula I, R.sup.1 represents H, C.sub.1-10 alkyl, C.sub.1-10 alkyl-D or C.sub.1-10 haloalkyl; R.sup.2 represents H, CH.sub.2N(CH.sub.3).sub.2 or CH.sub.2N(CD.sub.3).sub.2; and R.sup.4 represents ##STR00001##
or H, wherein X represents N, O or S; and L represents polypeptide, C.sub.1-20 linear alkyl or derivatives thereof, C.sub.1-20 linear or branched acyl derivatives, C.sub.2-100 ethylene glycol or derivatives thereof. The camptothecin derivatives have high solubility, the anticancer drugs prepared from them have the advantages of wide anticancer spectrum and high safety, and have in vivo anticancer activity higher than irinotecan hydrochloride.

The invention relates to novel camptothecin derivatives and their applications, tumor cell growth inhibitors, ternary complexes, and a method for improving the solubility of the camptothecin derivatives. The camptothecin derivatives are prepared by modifying the substance shown as Formula I with glycosylated triazole at position R.sup.3. In the structure shown as Formula I, R.sup.1 represents H, C.sub.1-10 alkyl, C.sub.1-10 alkyl-D or C.sub.1-10 haloalkyl; R.sup.2 represents H, CH.sub.2N(CH.sub.3).sub.2 or CH.sub.2N(CD.sub.3).sub.2; and R.sup.4 represents ##STR00001##
or H, wherein X represents N, O or S; and L represents polypeptide, C.sub.1-20 linear alkyl or derivatives thereof, C.sub.1-20 linear or branched acyl derivatives, C.sub.2-100 ethylene glycol or derivatives thereof. The camptothecin derivatives have high solubility, the anticancer drugs prepared from them have the advantages of wide anticancer spectrum and high safety, and have in vivo anticancer activity higher than irinotecan hydrochloride.

The invention relates to a low molecular weight sulfate chondroitin and a preparation method thereof. A low molecular weight chondroitin sulfate with the average molecular weight of less than 1000 Dalton can be obtained by a production process of chondroitin sulfate lyase degradation, deproteinization, filtration and sterilization and drying using macromolecular sulfate chondroitin as a raw material. The low molecular weight Chondroitin sulfate has a narrow molecular weight distribution range, the ratio of chondroitin sulfate disaccharide is 43˜60% and the ratio of chondroitin sulfate tetrasaccharide is 30˜45%, the sum of chondroitin sulfate disaccharide and chondroitin sulfate tetrasaccharide is more than 87%, the total oligosaccharide content of low molecular weight chondroitin sulfate is more than 97% and the protein content is less than 0.5%; Compared with the general market macromolecule chondroitin sulfate, the product has more remarkable repair effect at the concentration of 50˜100 μg/mL on chondrocytes damaged by 1 mM hydrogen peroxide, with strong repair ability and repair rate of 14%˜23%. The low molecular weight chondroitin sulfate can be used to treat joint injury and is an important raw material for medical products, health care products, cosmetics and food.

A lyophilized product of cyclic-di-AMP requires special production equipment and is thus not suitable for large-scale production. Crystals of cyclic-di-AMP free acid are unstable under severe conditions at 105° C. Then, the present invention addresses the problem of providing a cyclic-di-AMP crystal that can be easily acquired in a large amount and is very stable under the severe conditions at 105° C. Crystals of c-di-AMP sodium salt according to the present invention are extremely stable even under the severe conditions at 105° C. Further, the crystals of c-di-AMP sodium salt according to the present invention can be prepared in a large amount by a simple process including adjusting a c-di-AMP aqueous solution at pH 5.2-12.0 and then adding an organic solvent thereto.

A lyophilized product of cyclic-di-AMP requires special production equipment and is thus not suitable for large-scale production. Crystals of cyclic-di-AMP free acid are unstable under severe conditions at 105° C. Then, the present invention addresses the problem of providing a cyclic-di-AMP crystal that can be easily acquired in a large amount and is very stable under the severe conditions at 105° C. Crystals of c-di-AMP sodium salt according to the present invention are extremely stable even under the severe conditions at 105° C. Further, the crystals of c-di-AMP sodium salt according to the present invention can be prepared in a large amount by a simple process including adjusting a c-di-AMP aqueous solution at pH 5.2-12.0 and then adding an organic solvent thereto.

There are provided compounds of Formula I: ##STR00001##
various compositions thereof and methods for their use in the inhibition of α-amylase.

There are provided compounds of Formula I: ##STR00001##
various compositions thereof and methods for their use in the inhibition of α-amylase.