The present disclosure discloses prodrugs of gamma-hydroxybutyric acid as well as compositions and uses thereof.

The present disclosure discloses prodrugs of gamma-hydroxybutyric acid as well as compositions and uses thereof.

The present invention relates to compounds of formula (I) and to pharmaceutical compositions containing them:

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wherein meanings of the substituents are indicated in the description.

Such compounds for use in the treatment of cancer and other diseases related to altered angiogenesis, such as arthritic pathology, diabetic retinopathy, psoriasis and chronic inflammatory disease, are also within the scope of the present invention.

This application is directed to a compound of Formula II Also disclosed is a process for preparing a compound of Formula II comprising using the compounds of Formulae IV and V Also disclosed is a method for preparing a compound of Formula I comprising contacting a compound of Formula II with a compound of a compound of Formula VI wherein A.sup.1, A.sup.2 A.sup.3, R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4, B.sup.1, B.sup.2 and B.sup.3, are as defined in the disclosure.

##STR00001##

The present invention relates to the use of a pharmaceutically effective amount of an short-acting calcium channel blocking compound to treat ischemic heart conditions, cardiac arrhythmias, hypertensive crisis in an emergency room setting, hypertension before, during, or after surgery, no-reflow phenomenon following reperfusion, and diseases associated with decreased skeletal muscle blood flow. The invention also relates to pharmaceutical compositions formulated for use in such methods and to kits for such methods.

The present invention relates to the use of a pharmaceutically effective amount of an short-acting calcium channel blocking compound to treat ischemic heart conditions, cardiac arrhythmias, hypertensive crisis in an emergency room setting, hypertension before, during, or after surgery, no-reflow phenomenon following reperfusion, and diseases associated with decreased skeletal muscle blood flow. The invention also relates to pharmaceutical compositions formulated for use in such methods and to kits for such methods.

The invention provides an artificial sgRNA and a CRISPR/Cas9 system by combining the artificial sgRNA and Cas9. Activity of the sgRNA can be retained even when a nucleotide linker region for forming a single strand by linking the 3-terminal of crRNA and the 5-terminal of tracrRNA in sgRNA is substituted with an amino acid derivative linker, when the linker region existing between stem-loop 1 and stem-loop 2 of tracrRNA and/or the loop portion of stem-loop 2 are/is substituted with an amino acid derivative linker, or when an amino acid derivative linker is added/inserted into the vicinity of the 5-terminal and/or the 3-terminal of sgRNA. Stability in vivo can be improved by introducing one or more amino acid derivative linkers into the sgRNA.

The present disclosure discloses prodrugs of gamma-hydroxybutyric acid as well as compositions and uses thereof.

The present disclosure discloses prodrugs of gamma-hydroxybutyric acid as well as compositions and uses thereof.

The invention relates to the field of resolution of chiral compounds existing in the form of two optical antipodes (enantiomers), such as Baclofen. More particularly, the invention relates to the production of the pure enantiomer (R)() Baclofen, of chemical nomenclature (R)-4-amino-3-(4-chlorophenyl)-butanoic acid, and the hydrogen maleate salt thereof. More specifically, the invention relates to the resolution of hydrogen maleate salts of racemic Baclofen by preferential crystallisation and particularly by the AS3PC method (auto-seeded and programmed polythermal preferential crystallisation).