Abstract: The present invention provides a method of optimizing therapeutic efficacy and reducing toxicity associated with 6-mercaptopurine drug treatment of an immune-mediated gastrointestinal disorder such as inflammatory bowel disease. The method of the invention includes the step of determining the level of one or more 6-mercaptopurine metabolites in the patient having an immune-mediated gastrointestinal disorder.

Abstract: Hydrazino, oxyamino and carbonyl-based reagents and methods for incorporation into oligonucleotides during their solid phase synthesis are provided. Modified oligonucleotides are provided that incorporate the reagents provided here in. Immobilized oligonucleotides and oligonucleotide conjugates that contain covalent hydrazone or oxime linkages are provided. Methods for preparation of surface bound oligonucleotides are provided. Methods for the preparation of oligonucleotide conjugates are also provided.

Abstract: Disclosed are 6-hydroxyamino- or a 6-alkoxyamino-7-deazapurine-ribofuranose derivatives, salts, pharmaceutical compositions, and methods of use thereof for treating viral infections caused by a flaviviridae family virus, such as hepatitis C virus.

Abstract: The present invention provides new methods for the synthesis of the therapeutic dinucleotide, P1,P4-di(uridine 5?)-tetraphosphate, and demonstrates applicability to the production of large quantities. The methods of the present invention substantially reduce the time period required to synthesize diuridine tetraphosphate, preferably to three days or less. The novel tetrammonium and tetrasodium salts of P1,P4-di(uridine 5?)-tetraphosphate (Formula I) prepared by these methods are stable, soluble, nontoxic, and easy to handle during manufacture. wherein: X is Na, NH4 or H, provided that all X groups are not H.

Abstract: Linear cyclodextrin copolymers and linear oxidized cyclodextrin copolymers containing an unoxidized and/or an oxidized cyclodextrin moiety integrated into the polymer backbone are described. Methods of preparing such copolymers are also described. The linear cyclodextrin copolymer and linear oxidized cyclodextrin copolymer of the invention may be used as a delivery vehicle of various therapeutic agents.

Abstract: The present invention relates to processes for the preparation of any of the intermediate 1,3-substituted indenes of the formulae (Ia), (Ib) and (Ic) or a mixture thereof: wherein R1, R2, R3, R4, and R5 are defined herein. Compounds of formulae (Ia), (Ib) and (Ic) or mixtures thereof are useful in the preparation of compounds of formula (II): wherein R2, R3 and R6 are also defined herein.

Abstract: The present invention concerns novel C2,5?-disubstituted and N6?,C2,5?-trisubstituted adenosine derivatives and their different uses. These adenosine derivatives were found to be potent adenosine receptor agonists and thus are of a therapeutic value in the treatment and prophylaxis of diseases and disorders affected by adenosine receptor agonists.

Abstract: Disclosed herein are compounds of formula II: wherein Alk, Z, X1, X2, R1, —R10 and R11 are defined herein, and their salts and pharmaceutically acceptable derivatives thereof, as well as other compounds of the general formula Het-A-Alk-W-Ar-C(X2)?NO-X2 where Het, A, W and Ar are also defined herein. These compounds are useful in treating picornavirus infections in mammals. Novel intermediates of these compounds, as well as pharmaceutical compositions and methods of use, are also disclosed herein.

Abstract: A compound of the formula: wherein R1 is an aliphatic hydrocarbon group optionally having substituent(s), an aromatic hydrocarbon group optionally having substituent(s), a heterocyclic group optionally having substituent(s), a group of the formula: OR1a wherein R1a is a hydrogen atom or an aliphatic hydrocarbon group optionally having substituent(s), or a group of the formula: wherein R1b and R1c are the same or different and each is a hydrogen atom or an aliphatic hydrocarbon group optionally having substituent(s), X is a methylene group, a nitrogen atom, a sulfur atom or an oxygen atom, Y is an optionally substituted methylene group or an optionally substituted nitrogen atom, ring A is a 5 to 8-membered ring optionally substituted further by 1 to 4 substituent(s) selected from (1) an aliphatic hydrocarbon group optionally having substituent(s), (2) an aromatic hydrocarbon group optionally having substituent(s), (3) a group of the formula: OR2 wherein R2 is a hydrogen atom, or an aliphatic hydrocarb

Abstract: The isoquinoline compounds of formula (I) are VR1 antagonists that are useful in treating pain, inflammation, thermal hyperalgesia, urinary incontinence and bladder over activity. The “R”, “Z” and “L” variables are defined in the disclosure and the “X” variables are defined as follows: X1 is CR1; X2 is selected from the group consisting of N and CR2; X3 is selected from the group consisting of N and CR3; X4 is CR4; and X5 is selected from the group consisting of N and C.

Abstract: The present invention relates to 9-substituted adenine derivatives represented by formula (I) wherein W is selected from the group consisting of H, halogen, azido and amino group; X is selected from the group consisting of O, S, N(H), CH2, CH and C; Y is selected from the group consisting of H, hydroxy, C1-4 alkyl, C1-4 alkoxy and halogen; R is selected from the group consisting of H, hydroxymethyl, C1-4 alkyl, and C1-4 alkoxy; R1is selected from the group consisting of O, NH and CH2; R2represents a radical selected from the group consisting of —(CH2)n—S—C(O)—R4 and —(CH2)n—S—S—R4, where n=1-4 and R4is a C1-4-alkyl or aryl group and R4 is optionally substituted with a halogen, amino, N-alkylamino, N, N-dialkylamino or C1-4 alkoxy group and wherein each of the R2radicals may be the same or different; and R3is O or S. The derivatives are useful as prodrugs for inhibiting adenylyl cyclase and lowering 3?:5?-cAMP in cells, thereby inhibiting adenylyl cyclase dependent effects within cells.

Abstract: Synthetic processes are provided wherein oligomeric compounds are prepared having phosphodiester, phosphorothioate, phosphorodithioate, or other covalent linkages. The oligomers have substantially reduced exocyclic adducts deriving from acrylonitrile or related contaminants.

Abstract: The invention is directed to novel compositions and methods for nonenzymatic ligation of oligonucleotides. In one aspect of the invention, the nonenzymatic ligation is selenium-mediated or tellurium mediated ligation. In another aspect, the invention provides for the use of fluorescence resonance energy transfer (FRET) to detect the nonenzymatic ligation.

Abstract: Disclosed are A1 adenosine receptor agonists of the formula: wherein: R1 is optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; R2 is hydrogen, halo, trifluoromethyl, or cyano; R3 is hydrogen, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl, R4 and R5 are independently hydrogen or optionally substituted acyl; X is a covalent bond or lower alkylene optionally substituted by cycloalkyl; X1 is a covalent bond or alkylene; Y is a covalent bond or lower alkylene optionally substituted by hedroxy or cycloalkyl; and Z is —C?C—, —R6C?CR7—, or —CHR6CHR7—, in which R6 and R7 at each occurrence are hydrogen or lower alkyl.

Abstract: Methods of treating certain neurological diseases using exogenous uridine or a uridine source alone as a precursor of endogenous cytidine, particularly in the human brain, are disclosed. Methods are also disclosed wherein exogenous uridine or a uridine source is combined either with drugs increasing uridine availability or with compounds that serve as a source of choline in phospholipid synthesis.

Abstract: The present invention provides a method of optimizing therapeutic efficacy and reducing toxicity associated with 6-mercaptopurine drug treatment of an immune-mediated gastrointestinal disorder such as inflammatory bowel disease. The method of the invention includes the step of determining the level of one or more 6-mercaptopurine metabolites in the patient having an immune-mediated gastrointestinal disorder.

Abstract: A method for isolating nucleic acid which comprises: (a) applying a sample comprising cells containing nucleic acid to a filter, whereby the cells are retained as a retentate and contaminants are removed; (b) lysing the retentate from step (a) while the retentate is retained by the filter to form a cell lysate containing the nucleic acid; (c) filtering the cell lysate with the filter to retain the nucleic acid and remove remaining cell lysate; (d) optionally washing the nucleic acid retained by the filter; and (e) eluting the nucleic acid, wherein the filter composition and dimensions are selected so that the filter is capable of retaining the cells and the nucleic acid. Additionally, there is provided a substrate for lysing cells and purifying nucleic acid having a matrix and a coating and an integrity maintainer for maintaining the purified nucleic acid.

Abstract: This invention is directed to a method for treating a host infected with hepatitis B comprising administering an effective amount of an anti-HBV biologically active 2?-deoxy-?-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2?-deoxy-?-L-erythro-pentofuranonucleoside has the formula: wherein R is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate, or a phosphate derivative; and BASE is a purine or pyrimidine base which may be optionally substituted. The 2?-deoxy-?-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof may be administered either alone or in combination with another 2?-deoxy-?-L-erythro-pentofuranonucleoside or in combination with another anti-hepatitis B agent.

Abstract: Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence and bladder overactivity, wherein X1, X2, X3, X4, X5, R5, R6, R7, R8a, R8b, R9, Z1, Z2 and L are as defined in the description.

Abstract: Methods for the preparation of oligonucleotides having bioreversible phosphate blocking groups are disclosed. In one aspect, the present invention provides compounds comprising a sequence of nucleotide units that includes a first segment having at least one internucleoside linkage of formula: 3?-O—P(X)(O?)—O-5? and a second segment having at least one internucleoside linkage of formula: 3?-O—P(X)(Y1—(CH2)q—Y2—Y3—Z)—O-5? wherein each of X, Y1, and Y2 is, independently, O or S; q is 2 to about 4; Y3 is C(?O) or S; and Z is aryl having 6 to about 14 carbon atoms or alkyl having from one to about six carbon atoms.