The invention relates to fused cyclooctyne compounds, and to a method for their preparation. The invention also relates to a conjugate wherein a fused cyclooctyne compound according to the invention is conjugated to a label, and to the use of these conjugates in bioorthogonal labeling, imaging and/or modification, such as for example surface modification, of a target molecule. The invention further relates to a method for the modification of a target molecule, wherein a conjugate according to the invention is reacted with a compound comprising a 1,3-dipole or a 1,3-(hetero)diene.

The invention relates to a polypeptide comprising an amino acid having a bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN) group, particularly when said BCN group is present as: a residue of a lysine amino acid. The invention also relates to a method of producing a polypeptide comprising a BCN group, said method comprising genetically incorporating an amino acid comprising a BCN group into a polypeptide. The invention also relates to an amino acid comprising bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN), particularly and amino acid which is bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN) lysine. In addition the invention relates to a PylRS tRNA synthetase comprising the mutations Y271M, L274G and C313A.

Methods for making prodrugs of treprostinil and treprostinil derivatives are provided. Specifically, methods are provided herein for producing prostacyclin compounds comprising treprostinil covalently linked to a linear C.sub.5-C.sub.18 alkyl, branched C.sub.5-C.sub.18 alkyl, linear C.sub.2-C.sub.18 alkenyl, branched C.sub.3-C.sub.18 alkenyl, aryl, aryl-C.sub.1-C.sub.18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide). The linkage, in one embodiment, is via an amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. The compounds provided herein can be used to treat pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension.

Methods for making prodrugs of trepreostinil and treprostinil derivatives are provided. Specifically, methods are provided herein for producing prostacyclin compounds comprising treprostinil covalently linked to a linear C.sub.5-C.sub.18 alkyl, branched C.sub.5-C.sub.18 alkyl, linear C.sub.2-C.sub.18alkenyl, branched C.sub.3-C.sub.18alkenyl, aryl, aryl-C.sub.1-C.sub.18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide). The linkage, in one embodiment, is via an amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. The compounds provided herein can be used to treat pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension.

The present disclosure describes compounds of Formula (I) and pharmaceutically acceptable salts thereof:

##STR00001##

The disclosure provides chemical compounds possessing therapeutic and/or protective properties against oxidative damage. Methods of making such therapeutic and/or protective compounds and associated compositions are also provided, as are methods for their use, which include protecting cells from oxidative damage and/or inhibiting production of ROS in a cell or subject, as well as preventing or reducing the extent of tissue damage caused by an ischemic event in a subject at elevated risk of such an event.

The present disclosure relates to a multi- or dual-headed composition having the formula (I) or (II). The present disclosure also relates to a process for preparing the multi- or dual-headed composition having the formula (I) or (II), the process including combining 1,2,4-trivinylcyclochexane, an organometallic compound, and a catalyst precursor. The present disclosure further relates to use of the composition having the formula (I) or (II) in olefin polymerization.

The present invention relates to indane derivatives of the formula (I) and mixtures thereof, wherein X is selected from groups of the formulae -A-NH2 or -A-(NAr.sub.2), wherein A is a chemical bond or phenylene which is unsubstituted or substituted by 1, 2, 3 or 4 substituents selected from C.sub.1-C.sub.6 alkyl and C.sub.1-C.sub.6-alkoxy; Ar is unsubstituted or substituted aryl, wherein two groups Ar bound to the same nitrogen atom may together with the nitrogen atom also form a fused ring system having 3 or more than 3 unsubstituted or substituted rings; and the variables R.sup.A, R.sup.B, Y, k, I, m, p, q and r are as defined in the claims and the description. The invention further relates to methods for preparing such compounds and their use in organic electronics, in particular as hole transport material or electron blocking material.

##STR00001##

The present invention relates to vitamin D.sub.3 derivatives of the following formula, wherein each symbol has the same meaning as defined herein, and pharmaceutical or medical use thereof for treating metabolic disease, liver disease, obesity, diabetes, cardiovascular disease, or cancer in a patient in need thereof.

##STR00001##

Methods of preparing unsaturated compounds or analogs through dehydrogenation of corresponding saturated compounds and/or hydrogenation of aromatic compounds are disclosed.