The present invention relates to substituted alkynylene compounds represented by the compounds of formula (I), pharmaceutically acceptable salts and stereoisomers thereof. The present invention further provides the therapeutic uses of the compounds of formula (I) as anti-cancer agents.

Provided are novel prodrugs of treprostinil, as well as methods of making and methods of using these prodrugs.

Provided are novel prodrugs of treprostinil, as well as methods of making and methods of using these prodrugs.

The present invention is directed to a compound represented by Structural Formula (A):

##STR00001##

or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.

The present invention is directed to a compound represented by Structural Formula (A):

##STR00001##

or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.

Described herein are compounds and compositions characterized, in certain embodiments, by conjugation of various groups, such as lipophilic groups, to an amino or amide group of an amino acid, a linear or cyclic peptide, a linear or cyclic polypeptide, or structural isomer thereof, to provide compounds of the present invention, collectively referred to herein as “APPLs”. Such APPLs are deemed useful for a variety of applications, such as, for example, improved nucleotide delivery. Exemplary APPLs include, but are not limited to, compounds of Formula (I), (II), (III), (IV), (V), and (VI), and salts thereof, as described herein:

##STR00001##

wherein m, n, p, R′, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.8, Z, W, Y, and Z are as defined herein.

Described herein are compounds and compositions characterized, in certain embodiments, by conjugation of various groups, such as lipophilic groups, to an amino or amide group of an amino acid, a linear or cyclic peptide, a linear or cyclic polypeptide, or structural isomer thereof, to provide compounds of the present invention, collectively referred to herein as “APPLs”. Such APPLs are deemed useful for a variety of applications, such as, for example, improved nucleotide delivery. Exemplary APPLs include, but are not limited to, compounds of Formula (I), (II), (III), (IV), (V), and (VI), and salts thereof, as described herein:

##STR00001##

wherein m, n, p, R′, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.8, Z, W, Y, and Z are as defined herein.

The disclosure provides compounds of formula (I). The compounds may be used to degrade the Histone Deacetylase (HDAC) family of enzymes, particularly HDAC.sub.1, 2 and .sub.3 that exist in corepressor complexes. Accordingly, the compounds may be used to treat cancer. The invention extends to pharmaceutical compositions comprising these compounds, and the use of these compounds in therapy.

##STR00001##

The disclosure provides compounds of formula (I). The compounds may be used to degrade the Histone Deacetylase (HDAC) family of enzymes, particularly HDAC.sub.1, 2 and .sub.3 that exist in corepressor complexes. Accordingly, the compounds may be used to treat cancer. The invention extends to pharmaceutical compositions comprising these compounds, and the use of these compounds in therapy.

##STR00001##

A preparation method of a high-optical-purity chiral oxo-aza-cycloalkane compound comprises the steps of: (R or S)N-substituent P-2-alkoxycarbonylalkyliminodiacetic acid diester as the raw material is cyclized in the presence of a solvent and a cyclization reagent (lewis acid-lewis base) to obtain high-optical-purity N-substituent P -2- (R or S)- substituent G oxo-aza-cycloalkane or the salt thereof through thermal decarboxylation or hydrolysis decarboxylation reaction; the specific type of cyclization reagent used in the present invention is conductive to the preparation of the high-optical-purity target product, easily recoverable, with reduced waste liquid discharge, green, and environment-friendly, which contributes to green industrial production.