Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). The present invention reveals that quinacrine directly binds to G4 RNAs found in genomic RNA of the COVID-19 virus, showing antiviral activity against COVID-19 using in vitro cell culture systems. An object of the present invention is thus a new pharmaceutical composition of quinacrine for the treatment of COVID-19. Another object of the invention is a method for administering quinacrine by various routes specifically for treatment, including oral administration, sterile intravenous injection, and others.

Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). The present invention reveals that quinacrine directly binds to G4 RNAs found in genomic RNA of the COVID-19 virus, showing antiviral activity against COVID-19 using in vitro cell culture systems. An object of the present invention is thus a new pharmaceutical composition of quinacrine for the treatment of COVID-19. Another object of the invention is a method for administering quinacrine by various routes specifically for treatment, including oral administration, sterile intravenous injection, and others.

We disclose novel asymmetric bis-acridines with antitumour activity. These compounds are useful for use in pharmaceuticals, particularly in the treatment or the prevention of neoplasms.

The present invention provides therapeutic strategies for treatment of severe debilitating diseases associated with IFN-I due to cGAS activation. In one aspect, the invention provides compounds of Formula (I): [Formula should be inserted here] and pharmaceutical uses thereof. In another aspect, the invention provides methods for treating an autoimmune disease or a monogenic disorder by administering an effective amount of a compound of Formula (I).

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The present invention provides therapeutic strategies for treatment of severe debilitating diseases associated with IFN-I due to cGAS activation. In one aspect, the invention provides compounds of Formula (I): [Formula should be inserted here] and pharmaceutical uses thereof. In another aspect, the invention provides methods for treating an autoimmune disease or a monogenic disorder by administering an effective amount of a compound of Formula (I).

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Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):(I) or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A is a heterocyclic or heteroaryl ring, and R.sup.1, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, A, G.sup.1, G.sup.2, L.sup.1, L.sup.2, m.sup.1, m.sup.2, and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

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Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):(I) or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A is a heterocyclic or heteroaryl ring, and R.sup.1, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, A, G.sup.1, G.sup.2, L.sup.1, L.sup.2, m.sup.1, m.sup.2, and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

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The present invention relates to the compound having Formula (I) or pharmaceutically acceptable salts or solvates thereof, and its use in treating and/or preventing a Tauopathy.

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The present invention relates to the compound having Formula (I) or pharmaceutically acceptable salts or solvates thereof, and its use in treating and/or preventing a Tauopathy.

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The present invention relates to using a versatile synthetic approach to generate a new class of ester, amido, or carbamate prodrugs of highly potent, but systemically too toxic, platinum-acridine anticancer agents. The new hybrids contain a hydroxyl group, which has been masked with a cleavable lipophilic acyl moiety. Both butanoic (butyric) and bulkier 2-propanepentanoic (valproic) esters were introduced to these compounds. The goal of this design was to improve the drug-like properties of the pharmacophore (e. g., log D) without compromising its DNA-mediated cell kill potential. Two distinct pathways by which the target compounds undergo effective ester hydrolysis, the proposed activating step, have been confirmed: platinum-mediated, self-immolative ester cleavage in a low-chloride environment (LC-ESMS, NMR spectroscopy) and enzymatic cleavage by human carboxylesterase-2 (hCES-2) (LC-ESMS). Several of the new compounds show excellent stability, reduced systemic toxicity, and favorable activation profiles while maintaining submicromolar cytotoxicity in various cancers, such as lung adenocarcinoma cell lines (A549, NCI-H1435). The results suggest that the novel dual-mode prodrug concept may have the potential to hasten the preclinical development of platinum-acridines.