Treprostinil is a synthetic prostacyclin derivative with thrombocyte aggregation inhibitory and vasodilatory activity. Treprostinil can be administered in subcutaneous, intravenous, inhalable, or oral forms. Disclosed is a method for the preparation of treprostinil of formula I and its amorphous form, anhydrate form, monohydrate form, and polyhydrate form salts with bases. In the disclosed method, the chiral center in the 3-hydroxyoctyl substituent is formed at the end of the synthesis, so that the method is robust and well scalable. Also disclosed are treprostinil intermediates and the preparation of the intermediates.

##STR00001##

A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I: ##STR00001##
wherein X is —CH.sub.2—, —CH.sub.2—CH.sub.2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or ##STR00002##
A and B are independently selected from C and N; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently selected from —H, halogen, —OH, and —CH.sub.3; and R.sub.5, R.sub.6, and R.sub.7 are independently selected from —H, halogen, —OH, —OCH.sub.3, —NO.sub.2, —N(CH.sub.3).sub.2, C.sub.1-C.sub.6 alkyl, or a substituted or unsubstituted C.sub.4-C.sub.6 aryl group, except that when A and/or B is N the adjacent R.sub.5 and/or R.sub.7 is —H, or a pharmaceutically acceptable salt thereof.

A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I: ##STR00001##
wherein X is —CH.sub.2—, —CH.sub.2—CH.sub.2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or ##STR00002##
A and B are independently selected from C and N; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently selected from —H, halogen, —OH, and —CH.sub.3; and R.sub.5, R.sub.6, and R.sub.7 are independently selected from —H, halogen, —OH, —OCH.sub.3, —NO.sub.2, —N(CH.sub.3).sub.2, C.sub.1-C.sub.6 alkyl, or a substituted or unsubstituted C.sub.4-C.sub.6 aryl group, except that when A and/or B is N the adjacent R.sub.5 and/or R.sub.7 is —H, or a pharmaceutically acceptable salt thereof.

An improved chemical probe for the detection of the amino acid citrulline combines: 1) a reactive head formed of 1,3-dicarbonyl moiety that reacts with a citrulline side chain in an improved manner compared to currently used 1,2-dicarbonyl moieties; and 2) a modular action of the probe where citrulline side chains are labeled first using reactive heads described above, and attachment of a read-out subunit or tag, be it a fluorophore, a nanoparticle, or an antigen is performed separately. The modular nature of the chemical probe increases the sensitivity of the probes due to their smaller size. Additionally, the chemical probes of the present disclosure allow the same sample to be analyzed using a variety of read-out methods.

A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I:

##STR00001##

wherein X is —CH.sub.2—, —CH.sub.2—CH.sub.2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or

##STR00002##

A and B are independently selected from C and N; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently selected from —H, halogen, —OH, and —CH.sub.3; and R.sub.5, R.sub.6, and R.sub.7 are independently selected from —H, halogen, —OH, —OCH.sub.3, —NO.sub.2, —N(CH.sub.3).sub.2, C.sub.1-C.sub.6 alkyl, or a substituted or unsubstituted C.sub.4-C.sub.6 aryl group, except that when A and/or B is N the adjacent R.sub.5 and/or R.sub.7 is —H, or a pharmaceutically acceptable salt thereof.

A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I:

##STR00001##

wherein X is —CH.sub.2—, —CH.sub.2—CH.sub.2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or

##STR00002##

A and B are independently selected from C and N; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently selected from —H, halogen, —OH, and —CH.sub.3; and R.sub.5, R.sub.6, and R.sub.7 are independently selected from —H, halogen, —OH, —OCH.sub.3, —NO.sub.2, —N(CH.sub.3).sub.2, C.sub.1-C.sub.6 alkyl, or a substituted or unsubstituted C.sub.4-C.sub.6 aryl group, except that when A and/or B is N the adjacent R.sub.5 and/or R.sub.7 is —H, or a pharmaceutically acceptable salt thereof.

A phenalene-1-one compound, a photosensitizer composition including the phenalene-1-one compound, an article including the phenalene-1-one compound and/or photosensitizer composition and the use thereof.

A phenalene-1-one compound, a photosensitizer composition including the phenalene-1-one compound, an article including the phenalene-1-one compound and/or photosensitizer composition and the use thereof.

Treprostinil is a synthetic prostacyclin derivative with thrombocyte aggregation inhibitory and vasodilatory activity. Treprostinil can be administered in subcutaneous, intravenous, inhalable, or oral forms. Disclosed is a method for the preparation of treprostinil of formula I and its amorphous form, anhydrate form, monohydrate form, and polyhydrate form salts with bases. In the disclosed method, the chiral center in the 3-hydroxyoctyl substituent is formed at the end of the synthesis, so that the method is robust and well scalable. Also disclosed are treprostinil intermediates and the preparation of the intermediates. ##STR00001##

Treprostinil is a synthetic prostacyclin derivative with thrombocyte aggregation inhibitory and vasodilatory activity. Treprostinil can be administered in subcutaneous, intravenous, inhalable, or oral forms. Disclosed is a method for the preparation of treprostinil of formula I and its amorphous form, anhydrate form, monohydrate form, and polyhydrate form salts with bases. In the disclosed method, the chiral center in the 3-hydroxyoctyl substituent is formed at the end of the synthesis, so that the method is robust and well scalable. Also disclosed are treprostinil intermediates and the preparation of the intermediates. ##STR00001##