The present invention relates to compounds represented by formula (I) and formula (II) and a chiral synthesis and chiral isolation method therefor, further relating to a salt and crystal form of the compound represented by formula (I), a preparation method therefor, a pharmaceutical composition comprising the same, and use thereof in the preparation of a medicament used for the treatment of a viral infectious disease such as hepatitis B.

##STR00001##

It is provided a pentafluorophosphate derivative according to general formula (I):

##STR00001##

or a pharmaceutically acceptable salt or solvate thereof. Thereby, R.sup.1 and R.sup.2 denote independently from each other H or F; R.sup.3 denotes H, a C.sub.1-C.sub.10 alkyl optionally substituted by a hydrocarbon chain comprising an amide function and/or a carboxyl function, or by a substituent chosen from the group consisting of alkyl, alkylamino, alkylaminocarboxy, carboxy, alkoxycarbonyl, hydroxy, N-morpholino, N-morpholinoalkyl, N-morpholinocarbonyl, N-methyl-N-piperazinyl, N-methyl-N-piperazinylalkyl, N-methyl-N-piperazinylcarbonyl, and sulfo, an optionally substituted C.sub.3-C.sub.10 cycloalkyl, or an optionally substituted C.sub.6-C.sub.20 aryl, wherein a hydrocarbon chain of the alkyl, the cycloalkyl or the aryl can be interrupted by one or more oxygen, sulfur and/or nitrogen atoms; and M denotes any cation; with the proviso that at least one of R.sup.1 and R.sup.2 denotes F, if R.sup.3 denotes H.

The present disclosure involves a composition enriched in compound 61501b, wherein the compound 61501b has a purity of not less than 90% or more. The composition has a significant advantage in preparing a high-purity compound Sp-1. In addition, the present disclosure also provides a preparation method of the composition enriched in compound 61501b. The method adopts a crystallization technique to perform separation and purification, has a simple and convenient operation and good reproducibility, and therefore the compound 61501b in the prepared composition has high purity and quality. Further, the present disclosure also involves a novel crystal form of compound 61501b.

The present invention relates to a ligand compound, a catalyst system for olefin oligomerization and a method for oligomerizing an olefin using same. The catalyst system for olefin oligomerization according to the present invention exhibits high selectivity to 1-hexene or 1-octene while having excellent catalytic activity, thus enabling more efficient preparation of alpha-olefins.

The present invention relates to a ligand compound, a catalyst system for olefin oligomerization and a method for oligomerizing an olefin using same. The catalyst system for olefin oligomerization according to the present invention exhibits high selectivity to 1-hexene or 1-octene while having excellent catalytic activity, thus enabling more efficient preparation of alpha-olefins.

A crystalline form of phenyl bis (2,4,6-trimethylbenzoyl) phosphine oxide, with a large particle size, which belongs to a triclinic crystal system and space group P-1. A crystallization method for making the crystalline form of phenyl bis (2,4,6-trimethylbenzoyl) phosphine oxide, comprising adding a solid of phenyl bis (2,4,6-trimethylbenzoyl) phosphine oxide to a solvent and mixing; followed by heating to 50 to 70 C. to achieve complete dissolution; cooling the solution to room temperature; and adding an anti-solvent to the resulting solution to cause precipitation of crystals. The crystals are allowed to grow at a constant temperature for 10 to 60 minutes, so as to give a slurry containing the crystals. Said slurry is subjected to filtration and then drying to obtain the crystalline form of phenyl bis (2,4,6-trimethylbenzoyl) phosphine oxide.

Applicants have developed an amplification system and methodology for IHC and ISH staining that utilizes click chemistry to covalently bind reporter molecules to tissue.

The present invention provides compounds and pharmaceutical compositions of a peptidomimetic ligand, e.g. LLP2A, conjugated with a bisphosphonate drug, e.g. Alendronate. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of osteoporosis and for the promotion of bone growth due to their specificity for the .sub.4.sub.1 integrin on mesenchymal stem cells and for the surface of bone.

The present invention provides compounds and pharmaceutical compositions of a peptidomimetic ligand, e.g. LLP2A, conjugated with a bisphosphonate drug, e.g. Alendronate. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of osteoporosis and for the promotion of bone growth due to their specificity for the .sub.4.sub.1 integrin on mesenchymal stem cells and for the surface of bone.

The present invention relates to a novel crystalline hemihydrate polymorph of neridronic acid sodium salt, and a novel process for the preparation thereof comprising the steps of: 1) dissolving solid sodium neridronate in any crystalline form in water, at a temperature in the range from 70 to 90 C., to obtain an aqueous solution of sodium neridronate; 2) adding a solvent selected from the group consisting in ethanol, 1-propanol, and 2-propanol to the aqueous solution obtained from step (1), so that the final water:solvent volume ratio is in the range from 1:0.5 to 1:1, thus obtaining a suspension; 3) placing the suspension obtained from step (2) under mechanical stirring, at a temperature in the range from 60 to 95 C.; 4) recovering the crystalline hemihydrate form F of sodium neridronate formed in the previous step (3). The crystalline hemihydrate form F of sodium neridronate, particularly stable, may be employed in the preparation of solid oral pharmaceutical forms for use in the treatment of musculoskeletal and calcium metabolism disorders.