Abstract: The present invention provides prodrugs of GABA analogs, pharmaceutical compositions of prodrugs of GABA analogs and methods for making prodrugs of GABA analogs. The present invention also provides methods for using prodrugs of GABA analogs and methods for using pharmaceutical compositions of prodrugs of GABA analogs for treating or preventing common diseases and/or disorders.

Abstract: The present invention provides prodrugs of GABA analogs, pharmaceutical compositions of prodrugs of GABA analogs and methods for making prodrugs of GABA analogs. The present invention also provides methods for using prodrugs of GABA analogs and methods for using pharmaceutical compositions of prodrugs of GABA analogs for treating or preventing common diseases and/or disorders.

Abstract: This invention is directed to compounds that provide for sustained systemic concentrations of GABA analogs following administration to animals. This invention is also directed to pharmaceutical compositions including and methods using such compounds.

Abstract: This invention is directed to compounds that provide for sustained systemic concentrations of GABA analogs following administration to animals. This invention is also directed to pharmaceutical compositions including and methods using such compounds.

Abstract: The present invention provides prodrugs of GABA analogs, pharmaceutical compositions of prodrugs of GABA analogs and methods for making prodrugs of GABA analogs. The present invention also provides methods for using prodrugs of GABA analogs and methods for using pharmaceutical compositions of prodrugs of GABA analogs for treating or preventing common diseases and/or disorders.

Abstract: Methods of modifying therapeutic compounds such as drugs to be substrates for active transporters expressed in epithelial cells lining the lumen of the human colon are disclosed. The transporters expressed in the human colon include the sodium dependent multi-vitamin transporter (SMVT), and monocarboxylate transporters 1 and 4 (MCT 1 and MCT 4). The modified compounds can themselves be pharmacologically active, or upon cleavage of a chemical moiety after uptake from the colon, can be metabolized to form a compound that is pharmacologically active (e.g., a prodrug). The modified compounds disclosed herein are suitable for use in extended release oral dosage forms, particularly those that release drug over periods of greater than about 2-4 hours following administration.

Abstract: Disclosed herein are conjugates comprising a therapeutic agent (e.g., a drug) which is linked to a conjugate moiety that is itself, or itself in combination with the agent, is a good substrate for the sodium dependent multi-vitamin transporter (SMVT). The conjugates have a molecular weight below 1500 daltons and exhibit increased uptake via SMVT through the cells lining the gastrointestinal lumen, and hence higher bioavailability, when administered orally compared to the therapeutic agent itself Also disclosed are methods of delivering agents that, as a result of linkage to a conjugate moiety, are good substrates of the SMVT transporter. Further disclosed are methods of screening conjugates or conjugate moieties, linked or linkable to a therapeutic agent, for capacity to be transported as substrates through the SMVT transporter.

Abstract: The present invention provides an extended release oral dosage form of prodrugs of gabapentin and other GABA analogs, which dosage forms exhibit reduced toxicity. The dosage forms are particularly useful in administering those prodrugs of gabapentin and other GABA analogs that are metabolized to form an aldehyde. The dosage forms of the invention are useful for treating or preventing diseases and/or disorders for which the parent gabapentin or other GABA analog are known to be therapeutically effective.

Abstract: This invention is directed to methods for providing sustained systemic concentrations of therapeutic or prophylactic agents such as GABA analogs following oral administration to animals. This invention is also directed to compounds and pharmaceutical compositions that are used in such methods.

Abstract: Bile-acid conjugates useful for sustained release of L-DOPA, inhibitors of catechol O-methyl transferase and/or inhibitors of L-aromatic amino acid decarboxylase are provided.

Abstract: This invention is directed to compounds that provide for sustained systemic concentrations of therapeutic or prophylactic agents following administration to animals. This invention is also directed to pharmaceutical compositions including and methods using such compounds.

Abstract: This invention is directed to compounds that provide for sustained systemic concentrations of therapeutic or prophylactic agents following administration to animals. This invention is also directed to pharmaceutical compositions including and methods using such compounds.

Abstract: Disclosed are methods for providing sustained systemic blood concentrations of orally delivered drugs. Still further, disclosed are compounds and pharmaceutical compositions that are used in such methods.

Abstract: Disclosed are methods for providing enhanced systemic blood concentrations of orally delivered drugs that are incompletely translocated across the intestinal wall of an animal. Also disclosed are methods for the sustained release of drugs, whether poorly or readily bioavailable via oral delivery to animals. Still further, disclosed are compounds and pharmaceutical compositions that are used in such methods.

Abstract: Nucleotide analogs characterized by the presence of an amidate linked amino acid or an ester linked group which is bonded to the phosphorus atom of phosphonate nucleotide analogs are disclosed. The analogs comprise a phosphoamidate or ester bond that is hydrolyzed in vivo to yield a corresponding phosphonate nucleotide analog. Methods and intermediates for their synthesis and use are described.

Abstract: Nucleotide analogs characterized by the presence of an amidate linked amino acid or an ester linked group which is bonded to the phosphorus atom of phosphonate nucleotide analogs are disclosed. The analogs comprise a phosphoamidate or ester bond that is hydrolyzed in vivo to yield a corresponding phosphonate nucleotide analog. Methods and intermediates for their synthesis and use are described.

Abstract: Novel compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure --OC(R.sup.2).sub.2 OC(O)X(R).sub.a, wherein R.sup.2 independently is H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR.sup.3 in which R.sup.3 is C.sub.1 -C.sub.12 alkyl; X is N or O; R is independently H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro, --O--, --N.dbd., --NR.sup.4 --, --N(R.sup.4).sub.2 -- or OR.sup.3, R.sup.4 independently is --H or C.sub.1 -C.sub.

Abstract: Novel compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure -OC(R.sup.2).sub.2 OC(O) X(R).sub.a, wherein R.sup.2 independently is H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR.sup.3 in which R.sup.3 is C.sub.1 -C12 alkyl; X is N or O; R is independently H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, axido, nitro, --O--, --N.dbd., --NR.sup.4 --, --N(R.sup.4).sub.2 -- or OR.sup.3, R.sup.4 independently is --H or C.sub.1 -C.sub.

Abstract: Compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure --OC(R.sup.2).sub.2 OC(O)X(R).sub.a, wherein R.sup.2 independently is H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR.sup.3 in which R.sup.3 is C.sub.1 -C.sub.12 alkyl; X is N or O; R is independently H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro, --O--, --N.dbd., --NR.sup.4 --, --N(R.sup.4).sub.2 -- or OR.sup.3, R.sup.4 independently is --H or C.sub.1 -C.sub.

Abstract: Novel compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure —OC(R2)2OC(O)X(R)a, wherein R2 independently is H, C1-C12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR3 in which R3 is C1-C12 alkyl; X is N or O; R is independently H, C1-C12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro, —O—, —N═, —NR4—, —N(R4)2— or OR3, R4 independently is —H or C1-C8 alkyl, provided that at least one R is not H; and a is 1 or 2, with the proviso that when a is 2 and X is N, (a) two R groups can be taken together to form a carbocycle or oxygen-containing heterocycle, or (b) one R additionally can be OR3.