The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

The disclosure provides Group 6 complexes, which, in some embodiments, are useful for catalyzing olefin metathesis reactions. In some embodiments, the compounds are compounds of the following formula:

##STR00001##

wherein: M is a Group 6 metal atom; X is an oxygen atom, ═N—R.sup.5, ═N—N(R.sup.5)(R.sup.5′) or ═N—O—R.sup.5, R.sup.5 and R.sup.5′ independently being various substituents, such as aryl or heteroaryl, each optionally substituted; n is 0 or 1; R.sup.z is a neutral ligand; R.sup.1 is hydrogen or an organic substituent; R.sup.2 is an aryl or heteroaryl group, each optionally substituted; R.sup.3 is an anionic ligand; and R.sup.4 is an anionic ligand, such as a pyrrolide, a pyrazolide, an imidazolide, an indolide, an azaindolide, or an indazolide, each optionally substituted.

The disclosure provides Group 6 complexes, which, in some embodiments, are useful for catalyzing olefin metathesis reactions. In some embodiments, the compounds are compounds of the following formula:

##STR00001##

wherein: M is a Group 6 metal atom; X is an oxygen atom, ═N—R.sup.5, ═N—N(R.sup.5)(R.sup.5′) or ═N—O—R.sup.5, R.sup.5 and R.sup.5′ independently being various substituents, such as aryl or heteroaryl, each optionally substituted; n is 0 or 1; R.sup.z is a neutral ligand; R.sup.1 is hydrogen or an organic substituent; R.sup.2 is an aryl or heteroaryl group, each optionally substituted; R.sup.3 is an anionic ligand; and R.sup.4 is an anionic ligand, such as a pyrrolide, a pyrazolide, an imidazolide, an indolide, an azaindolide, or an indazolide, each optionally substituted.

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.

The present invention provides a process for preparing a dimethylcyclobutane compound of the following general formula (1A), the process comprising reacting a dimethylcyclobutanone compound of the following general formula (2) with a phosphonic ester compound of the following general formula (3) to produce an unsaturated ester compound of the following general formula (4), having a dimethylcyclobutane ring, and subjecting the unsaturated ester compound (4), having a dimethylcyclobutane ring, to a reduction reaction to produce the dimethylcyclobutane compound (1A).

##STR00001##

The present invention provides a process for preparing a diester compound of the following general formula (1), having a dimethylcyclobutane ring, wherein R.sup.1 and R.sup.2 represent, independently of each other, a monovalent hydrocarbon group having 1 to 10 carbon atoms, the process comprising reacting a dimethylcyclobutanone compound of the following general formula (2), wherein R.sup.1 is as defined above, with a phosphonic ester compound of the following general formula (3), wherein R.sup.2 and R.sup.3 represent, independently of each other, a monovalent hydrocarbon group having 1 to 10 carbon atoms, to produce the diester compound (1), having a dimethylcyclobutane ring.

##STR00001##