Provided herein are processes for synthesizing Mcl-1 inhibitors and intermediates such as compound F that can be used to prepare them where the variable PG is as defined herein. In particular, provided herein are processes for synthesizing compound A1, and salts or solvates thereof and compound A2, and salts and solvates thereof.

##STR00001##

An especially robust compound and its derivative metal complexes that are approximately one hundred-fold superior in catalytic performance to the previously invented TAML analogs is provided having the formula (I) wherein Y.sub.1, Y.sub.2, Y.sub.3 and Y.sub.4 are oxidation resistant groups which are the same or different and which form 5- or 6-membered rings with a metal, M, when bound to D; at least one Y incorporates a group that is significantly more stable towards nucleophilic attack than the organic amides of TAML activators; D is a metal complexing donor atom, preferably N; each X is a position for addition of a labile Lewis acidic substituent such as (i) H, deuterium, (ii) Li, Na, K, alkali metals, (iii) alkaline earth metals, transition metals, rare earth metals, which may be bound to one or more than one D, (iv) or is unoccupied with the resulting negative charge being balanced by a nonbonded counter-action; at least one Y may contain a site that is labile to acid dissociation, providing a mechanism for shortening complex lifetime. The new complexes deliver catalytic performances that promise to revolutionize multiple oxidation technology spaces including water purification. ##STR00001##

An especially robust compound and its derivative metal complexes that are approximately one hundred-fold superior in catalytic performance to the previously invented TAML analogs is provided having the formula (I) wherein Y.sub.1, Y.sub.2, Y.sub.3 and Y.sub.4 are oxidation resistant groups which are the same or different and which form 5- or 6-membered rings with a metal, M, when bound to D; at least one Y incorporates a group that is significantly more stable towards nucleophilic attack than the organic amides of TAML activators; D is a metal complexing donor atom, preferably N; each X is a position for addition of a labile Lewis acidic substituent such as (i) H, deuterium, (ii) Li, Na, K, alkali metals, (iii) alkaline earth metals, transition metals, rare earth metals, which may be bound to one or more than one D, (iv) or is unoccupied with the resulting negative charge being balanced by a nonbonded counter-action; at least one Y may contain a site that is labile to acid dissociation, providing a mechanism for shortening complex lifetime. The new complexes deliver catalytic performances that promise to revolutionize multiple oxidation technology spaces including water purification. ##STR00001##

An especially robust compound and its derivative metal complexes that are approximately one hundred-fold superior in catalytic performance to the previously invented TAML analogs is provided having the formula (I) wherein Y.sub.1, Y.sub.2, Y.sub.3 and Y.sub.4 are oxidation resistant groups which are the same or different and which form 5- or 6-membered rings with a metal, M, when bound to D; at least one Y incorporates a group that is significantly more stable towards nucleophilic attack than the organic amides of TAML activators; D is a metal complexing donor atom, preferably N; each X is a position for addition of a labile Lewis acidic substituent such as (i) H, denterium, (ii) Li, Na, K, alkali metals, (iii) alkaline earth metals, transition metals, rare earth metals, which may be bound to one or more than one D, (iv) or is unoccupied with the resulting negative charge being balanced by a nonhonded counter-action; at least one Y may contain a site that is labile to acid dissociation, providing a mechanism for shortening complex lifetime. The new complexes deliver catalytic performances that promise to revolutionize multiple oxidation technology spaces including water purification.

##STR00001##

An especially robust compound and its derivative metal complexes that are approximately one hundred-fold superior in catalytic performance to the previously invented TAML analogs is provided having the formula (I) wherein Y.sub.1, Y.sub.2, Y.sub.3 and Y.sub.4 are oxidation resistant groups which are the same or different and which form 5- or 6-membered rings with a metal, M, when bound to D; at least one Y incorporates a group that is significantly more stable towards nucleophilic attack than the organic amides of TAML activators; D is a metal complexing donor atom, preferably N; each X is a position for addition of a labile Lewis acidic substituent such as (i) H, denterium, (ii) Li, Na, K, alkali metals, (iii) alkaline earth metals, transition metals, rare earth metals, which may be bound to one or more than one D, (iv) or is unoccupied with the resulting negative charge being balanced by a nonhonded counter-action; at least one Y may contain a site that is labile to acid dissociation, providing a mechanism for shortening complex lifetime. The new complexes deliver catalytic performances that promise to revolutionize multiple oxidation technology spaces including water purification.

##STR00001##

A subject of the present invention is the use of a compound having the general formula (I): (I) wherein V, W, X.sub.4, X.sub.5, X.sub.6, X.sub.7, X.sub.4, X.sub.5, X.sub.6, X.sub.7, Y, Y, R.sub.3, R.sub.3, R.sub.4 and R.sub.4 are as defined in any one of claims 1 to 11, for the detection, capture and/or separation of polluting gases, in particular those selected from the group comprising carbon dioxide, methane, sulfur dioxide, nitrogen oxides, carbon monoxide, linear hydrocarbons, linear mono-olefins and their mixtures, and preferably carbon dioxide. Another subject of the invention is a compound of formula (I) wherein V, W, X.sub.4, X.sub.5, X.sub.6, X.sub.7, X.sub.4, X.sub.5, X.sub.6, X.sub.7, Y, Y, R.sub.3, R.sub.3, R.sub.4 and R.sub.4 are as defined in any one of claims 12 to 21. ##STR00001##

A subject of the present invention is the use of a compound having the general formula (I): (I) wherein V, W, X.sub.4, X.sub.5, X.sub.6, X.sub.7, X.sub.4, X.sub.5, X.sub.6, X.sub.7, Y, Y, R.sub.3, R.sub.3, R.sub.4 and R.sub.4 are as defined in any one of claims 1 to 11, for the detection, capture and/or separation of polluting gases, in particular those selected from the group comprising carbon dioxide, methane, sulfur dioxide, nitrogen oxides, carbon monoxide, linear hydrocarbons, linear mono-olefins and their mixtures, and preferably carbon dioxide. Another subject of the invention is a compound of formula (I) wherein V, W, X.sub.4, X.sub.5, X.sub.6, X.sub.7, X.sub.4, X.sub.5, X.sub.6, X.sub.7, Y, Y, R.sub.3, R.sub.3, R.sub.4 and R.sub.4 are as defined in any one of claims 12 to 21. ##STR00001##

The disclosure provides for compounds having immunoproteasome inhibitory activity, and pharmaceutical compositions made thereof. The disclosure further provides for the use of the compounds and compositions in treating various diseases and disorders in a subject that are associated with immunoproteasome activity, including inflammatory disorders, autoimmune disorders, hematological disorders, and neurodegenerative disorders.

The disclosure provides for compounds having immunoproteasome inhibitory activity, and pharmaceutical compositions made thereof. The disclosure further provides for the use of the compounds and compositions in treating various diseases and disorders in a subject that are associated with immunoproteasome activity, including inflammatory disorders, autoimmune disorders, hematological disorders, and neurodegenerative disorders.

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, thereof:

##STR00001##

which inhibit coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and methods of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.