Inhibitors of SARS-CoV-2 (COVID), pharmaceutical compositions comprising same; and methods of treating a severe acute respiratory syndrome.

The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.

Disclosed herein are compounds of formula (I)

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and therapeutic methods of treatment with compounds of formula (I), wherein L.sup.1, L.sup.2, L.sup.4, R.sup.1, R.sup.4, R.sup.5, R.sup.6, and s are as defined in the specification. Compounds of formula (I) are EP4 agonists useful in the treatment of glaucoma, neuropathic pain, and related disorders.

Disclosed herein are compounds of formula (I)

##STR00001##

and therapeutic methods of treatment with compounds of formula (I), wherein L.sup.1, L.sup.2, L.sup.4, R.sup.1, R.sup.4, R.sup.5, R.sup.6, and s are as defined in the specification. Compounds of formula (I) are EP4 agonists useful in the treatment of glaucoma, neuropathic pain, and related disorders.

The present invention relates to novel compounds of general Formula II:

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wherein the groups X, and R.sup.1 to R.sup.4 have the meanings given in the description, to a process for preparing these compounds and to their use for treating, preventing or ameliorating viral infections and diseases which are associated with PLA2G16.

The present invention relates to novel compounds of general Formula II:

##STR00001##

wherein the groups X, and R.sup.1 to R.sup.4 have the meanings given in the description, to a process for preparing these compounds and to their use for treating, preventing or ameliorating viral infections and diseases which are associated with PLA2G16.

The invention provides heterocyclic compounds with quaternary centers and methods of preparing compounds. Methods include the method for the preparation of a compound of Formula (II):

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comprising treating a compound of Formula (I):

##STR00002##

with a transition metal catalyst and under alkylation conditions as valence and stability permit.

The invention provides heterocyclic compounds with quaternary centers and methods of preparing compounds. Methods include the method for the preparation of a compound of Formula (II):

##STR00001##

comprising treating a compound of Formula (I):

##STR00002##

with a transition metal catalyst and under alkylation conditions as valence and stability permit.

Provided herein are compounds of Formula (I), their pharmaceutically acceptable salts, and their pharmaceutical compositions:

##STR00001##

wherein R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4, R.sup.5, and A are defined in the present disclosure. The compounds are potent inhibitors of the main protease (M.sup.pro) of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), and they are useful in treating or preventing COVID-19 in a subject.

Provided herein are compounds of Formula (I), their pharmaceutically acceptable salts, and their pharmaceutical compositions:

##STR00001##

wherein R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4, R.sup.5, and A are defined in the present disclosure. The compounds are potent inhibitors of the main protease (M.sup.pro) of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), and they are useful in treating or preventing COVID-19 in a subject.