Disclosed herein, inter alia, are acyclic nucleotide analogs and methods of using an acyclic nucleotide analog for treating and/or ameliorating a papillomavirus infection.

Compounds represented by Formula (I) and (II) and salts thereof are described herein. The compounds or salts of Formula (I) and (II) may be used to treat senescence-associated diseases and disorders.

##STR00001##

An object t of the present invention is to proroaide crystal of a cyclic phosphonic acid sodium salt (2ccPA) with high purity and excellent storage stability and a method for producing the crystal. The present invention provides a crystal of a cyclic phosphonic acid sodium salt (2ccPA) represented by formula (1): ##STR00001##

An object t of the present invention is to provide crystal of a cyclic phosphonic acid sodium salt (2ccPA) with high purity and excellent storage stability and a method for producing the crystal. The present invention provides a crystal of a cyclic phosphonic acid sodium salt (2ccPA) represented by formula (1):

##STR00001##

An object of the present invention is to provide crystal of a cyclic phosphonic acid sodium salt (2ccPA) with high purity and excellent storage stability and a method for producing the crystal. The present invention provides a crystal of a cyclic phosphonic acid sodium salt (2ccPA) represented by formula (1):

##STR00001##

A method of making a phosphono-phosphate compound is disclosed. The method involves a first step of mixing a first component comprising a phosphonic acid, a phosphonate or mixtures thereof, with a second component comprising a source of phosphoric acid or phosphate. The mixture has a molar phosphorous ratio of the first component to the second component of from 1:1 to 1:10. The second step involves either physically or chemically dehydrating the mixture to produce a phosphono-phosphate compound.

Provided are a compound for treating metabolic diseases having the structure as shown in formula (I) or formula (II), or a racemate, stereoisomer, geometric isomer, tautomer, solvate, hydrate, metabolite, pharmaceutically acceptable salt or prodrug thereof. The compound is an activator of FXR and/or a TGR5 receptor, and thus has the activity of activating FXR and/or a TGR5 receptor, and can be used in the preparation of drugs for treating chronic liver diseases, metabolic diseases or portal hypertension.

Provided herein are N-heterocyclic phosphines (NHPs) useful in metal-free phosphorus-carbon bond forming reactions. Methods for preparing vinylphosphonates using NHPs also are provided. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Compounds are of the formula (Ia), (Ib), (Ic), or are stereoisomers thereof, wherein: R1 is hydrogen, (C1-C20)alkyl; (C3-C20)alkenyl; (C3 C20)alkynyl; (C1-C6)alkyl-O; (C3-C20)cycloalkyl; (C1 C20)haloalkyl; (C6-C20)aryl optionally substituted; (C6-C20)heteroaryl optionally substituted; R2 and R2 are hydrogen; (C1-C20)alkyl; (C1-C6)alkyl-O; (C1-C6)haloalkyl; halogen; cyano; and nitro; Z1 to Z4 are diradicals of formula (III) wherein A1 and A2 are O or NR3-, wherein R3 is selected from the group consisting of hydrogen and (C1-C20)alkyl; and G is (C1-C6)alkyl; P(S)R5-; P(O)R4; P(O)(OR4)-; P(O)(NR6R7)-; S(O)2-; S(O); or C(O); and Y1 to Y4 are (C1-C8)alkyl; (C3-C7)cycloalkyl; (C6-C20)aryl optionally substituted; or (C6-C20)heteroaryl optionally substituted; and FG1 and FG2 are H, OH, or NHR8.

The present invention relates to novel phosphonoamidate prodrugs. The invention also relates to the use of these novel phosphonate-modified nucleosides to treat or prevent viral infections and their use to manufacture a medicine to treat or prevent viral infections, particularly infections with viruses such as the herpes simplex virus 1, herpes simplex virus 2, human cytomegalovirus, varicella zoster virus, vaccinia virus and adenovirus.