Patent classifications
C07F9/24
GAMMA-HYDROXYBUTYRATE DELIVERING COMPOUNDS AND PROCESSES FOR MAKING AND USING THEM
Disclosed are one or more compounds comprising chemically modified gamma-hydroxybutyrate (GHB), 2-hydroxytetrahydrofuran, and/or 1,4-butanediol, and salts of such compounds (GHB delivering compounds and salts thereof). Also disclosed are compositions comprising at least one GHB delivering compound, or a salt thereof, methods of making such compounds, and methods of using such GHB delivering compounds and compositions. Methods of treatment using the compounds are also disclosed.
DIOXOLANE ANALOGUES OF URIDINE FOR THE TREATMENT OF CANCER
The invention provides compounds of the formula:
##STR00001## R.sup.1 is OR.sup.11, or NR.sup.5R.sup.5′; R.sup.2 is H or F; R.sup.5 is H, C.sub.1-C.sub.6alkyl, OH, C(═O)R.sup.6, O(C═O)R.sup.6 or O(C═O)OR.sup.6; R.sup.5′ is H or C.sub.1-C.sub.6alkyl; R.sup.6 is C.sub.1-C.sub.6alkyl or C.sub.3-C.sub.7cycloalkyl; R.sup.13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R.sup.22;
and the other variables are as defined in the claims,
which are of use in the treatment of cancer, and related aspects.
DIOXOLANE ANALOGUES OF URIDINE FOR THE TREATMENT OF CANCER
The invention provides compounds of the formula:
##STR00001## R.sup.1 is OR.sup.11, or NR.sup.5R.sup.5′; R.sup.2 is H or F; R.sup.5 is H, C.sub.1-C.sub.6alkyl, OH, C(═O)R.sup.6, O(C═O)R.sup.6 or O(C═O)OR.sup.6; R.sup.5′ is H or C.sub.1-C.sub.6alkyl; R.sup.6 is C.sub.1-C.sub.6alkyl or C.sub.3-C.sub.7cycloalkyl; R.sup.13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R.sup.22;
and the other variables are as defined in the claims,
which are of use in the treatment of cancer, and related aspects.
Dioxolane analogues of uridine for the treatment of cancer
The invention provides compounds of the formula: ##STR00001## R.sup.1 is OR.sup.11, or NR.sup.5R.sup.5′; R.sup.2 is H or F; R.sup.5 is H, C.sub.1-C.sub.6alkyl, OH, C(═O)R.sup.6, O(C═O)R.sup.6 or O(C═O)OR.sup.6; R.sup.5′ is H or C.sub.1-C.sub.6alkyl; R.sup.6 is C.sub.1-C.sub.6alkyl or C.sub.3-C.sub.7cycloalkyl; R.sup.13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R.sup.22;
and the other variables are as defined in the claims,
which are of use in the treatment of cancer, and related aspects.
Dioxolane analogues of uridine for the treatment of cancer
The invention provides compounds of the formula: ##STR00001## R.sup.1 is OR.sup.11, or NR.sup.5R.sup.5′; R.sup.2 is H or F; R.sup.5 is H, C.sub.1-C.sub.6alkyl, OH, C(═O)R.sup.6, O(C═O)R.sup.6 or O(C═O)OR.sup.6; R.sup.5′ is H or C.sub.1-C.sub.6alkyl; R.sup.6 is C.sub.1-C.sub.6alkyl or C.sub.3-C.sub.7cycloalkyl; R.sup.13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R.sup.22;
and the other variables are as defined in the claims,
which are of use in the treatment of cancer, and related aspects.
Solid supports and phosphoramidite building blocks for oligonucleotide conjugates
Novel non-nucleoside solid supports and phosphoramidite building blocks for preparation of synthetic oligonucleotides containing at least one non-nucleosidic moiety conjugated to a ligand of practical interest and synthetic processes for making the same are disclosed. Furthermore, oligomeric compounds are prepared using said solid supports and phosphoramidite building blocks, preferably followed by removal of protecting groups to provide oligonucleotides conjugated to ligands of interest.
Site-specific generation of phosphorylated tyrosines in proteins
Provided herein are novel materials and methods for site-specific incorporation of phosphotyrosines into proteins. The novel methods of the invention encompass the use of a novel aminoacyl tRNA synthetase capable of charging compatible tRNAs with a phosphotyrosine precursor. The phosphotyrosine precursor is then incorporated, site-specifically, into a protein at sites where phosphotyrosine residues are desired. The phosphotyrosine precursors are subsequently treated to convert them into phosphotyrosine residues, yielding proteins with phosphotyrosines at selected sites. The scope of the invention encompasses novel aminoacyl tRNA synthetases, novel phosphotyrosine precursors, and methods of using these materials to create site-specific phosphorylated tyrosine residues in a protein.
Reagents useful for synthesizing rhodamine-labeled oligonucleotides
The present disclosure provides reagents that can be used to label synthetic oligonucleotides with rhodamine dyes or dye networks that contain rhodamine dyes.
PROGRAMMABLE POLYMERIC DRUGS
Compounds useful as biologically active compounds are disclosed. The compounds have the following structure (I):
##STR00001##
or a stereoisomer, tautomer or salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, L, L.sup.1, L.sup.2, L.sup.3, M and n are as defined herein. Methods associated with preparation and use of such compounds is also provided.
Methods of Making High Enantioselective Secondary Alcohols
A new process to synthesis of compound OBI-3424 R-form and S-form products is provided. The “R-form” compound OBI-3423 was first synthesized with 48% overall yield from compound OBI-3424-5 by installation of the labile phosphate motif at later stage. The stereo chemistry is established by 5 steps chemo-enzyme combination synthesis to afford 99% optical purity. After then, the “S-form” compound OBI-3424 is prepared with improving overall yield of 54% from compound OBI-3424-5. The stereo chemistry is established by 4 steps combination of chemo-enzyme synthesis with excellent optical purity of 99%.