Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.

Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.

The present invention relates to compounds of formula (I);

##STR00001##

for use as peripheral NMDA receptor antagonists.

The present invention relates to compounds of formula (I);

##STR00001##

for use as peripheral NMDA receptor antagonists.

The invention provides cereblon binders of Formulas: ##STR00001##
or pharmaceutically acceptable salts thereof, for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway along with their use in therapeutic applications to treat medical disorders including, but not limited to cancer.

One aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, (I) wherein: ring A is a 5 or 6 membered aromatic or heteroaromatic ring, wherein said aromatic or heteroaromatic ring is optionally substituted with one or more substituents selected from F, Cl, Br, I, CN, alkoxy, NR.sub.11R.sub.11′, OH, alkyl, haloalkyl, aralkyl, aryl, and heteroaryl, and wherein said aryl and heteroaryl substituents are in turn optionally substituted with one or more substituents each independently selected from F, Cl, Br, I, CN, alkoxy, NR.sub.11R.sub.11′, OH, alkyl, haloalkyl, and aralkyl; Y is selected from C═N—OH and CR10R.sub.10′, wherein R.sub.10 and R.sub.10′, are each independently selected from H, F, alkyl, and haloalkyl; R.sub.1, R.sub.4, and R.sub.5 are each independently selected from H, F, Cl, Br, and I; R.sub.2 and R.sub.3 are each independently selected from H, F, Cl, Br, I, CN, methoxy, and haloalkyl; and R.sub.11 and R.sub.11′ wherein R.sub.12 and R.sub.13 are both alkyl; for use as a medicament. Further aspects of the invention relate to compounds of formula (I) for use in the field of immuno-oncology, immunology, and related applications, and compounds of formula (I) per se.

##STR00001##

One aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, (I) wherein: ring A is a 5 or 6 membered aromatic or heteroaromatic ring, wherein said aromatic or heteroaromatic ring is optionally substituted with one or more substituents selected from F, Cl, Br, I, CN, alkoxy, NR.sub.11R.sub.11′, OH, alkyl, haloalkyl, aralkyl, aryl, and heteroaryl, and wherein said aryl and heteroaryl substituents are in turn optionally substituted with one or more substituents each independently selected from F, Cl, Br, I, CN, alkoxy, NR.sub.11R.sub.11′, OH, alkyl, haloalkyl, and aralkyl; Y is selected from C═N—OH and CR10R.sub.10′, wherein R.sub.10 and R.sub.10′, are each independently selected from H, F, alkyl, and haloalkyl; R.sub.1, R.sub.4, and R.sub.5 are each independently selected from H, F, Cl, Br, and I; R.sub.2 and R.sub.3 are each independently selected from H, F, Cl, Br, I, CN, methoxy, and haloalkyl; and R.sub.11 and R.sub.11′ wherein R.sub.12 and R.sub.13 are both alkyl; for use as a medicament. Further aspects of the invention relate to compounds of formula (I) for use in the field of immuno-oncology, immunology, and related applications, and compounds of formula (I) per se.

##STR00001##

The present invention relates to compounds of formula (I):

##STR00001##

for use as peripheral NMDA receptor antagonists.

The present invention relates to compounds of formula (I):

##STR00001##

for use as peripheral NMDA receptor antagonists.

A method administers quaternary ammonium anti-cholinergic muscarinic receptor antagonists in combination with acetyl-cholinesterase inhibitors to treat either cognitive impairment or acute delirium. This therapy results in a modification of a cognitive disorder or disease, namely a slow down in the disease progression. In one preferred embodiment, the disease is dementia with Lewy Bodies. New formulations for quaternary ammonium anti-cholinergic muscarinic receptor antagonists are also disclosed.