Disclosed is a biarylamide compound as a Pan-RAF kinase inhibitor, and specifically disclosed are a compound as shown in formula (III) and a pharmaceutically acceptable salt thereof.

##STR00001##

Protected fluorescent reagent compounds and their methods of synthesis are provided. The compounds are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The compounds contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements.

Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.

The present invention relates to phosphate derivatives of formula (I), and their therapeutic uses, preferably for treating a respiratory disease. The present invention further relates to pharmaceutical compositions and devices comprising such compounds.

This invention provides for prodrug Compounds I, pharmaceutical compositions thereof, and their use in treating HIV infection.

##STR00001## wherein: X is C or N with the proviso that when X is N, R.sup.1 does not exist; W is C or N with the proviso that when W is N, R.sup.2 does not exist; V is C; E is hydrogen or a pharmaceutically acceptable salt thereof; and Y is selected from the group consisting of

##STR00002##

Also, this invention provides for intermediate Compounds II useful in making prodrug Compounds I.

##STR00003## wherein: L and M are independently selected from the group consisting of C.sub.1-C.sub.6 alkyl, phenyl, benzyl, trialkylsilyl, -2,2,2-trichloroethoxy and 2-trimethylsilylethoxy.

The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Horner-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.

The disclosure relates to compounds of Formulae (I)-(IX), which are formyl peptide 2 (FPR2) receptor agonists and/or formyl peptide 1 (FPR1) receptor agonists. The disclosure also provides compositions and methods of using the compounds, for example, for the treatment of atherosclerosis, heart failure, chronic obstructive pulmonary disease (COPD), and related diseases. ##STR00001##

The present invention relates to inorganic salts of nicotinic acid mononucleotides and compositions of Formula I, useful in the treatment of disorders and diseases associated with deficiencies in NAD.sup.+:

##STR00001##

wherein A, M.sup.1, M.sup.2, k, R.sup.1, R.sup.2, and R.sup.3 are as described herein.

Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.

The present invention relates to an oligonucleotide comprising at least one phosphorodithioate internucleoside linkage of formula (I) (I) as defined in the description and in the claim. The oligonucleotide of the invention can be used as a medicement.

##STR00001##