The present invention relates to pyridazinones and related compounds which are inhibitors of PARP7 and are useful in the treatment of cancer.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The invention provides a compound of Formula I:

##STR00001##

or a pharmaceutically acceptable salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of Formula I, processes for preparing compounds of Formula I, therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS symptoms in a mammal using compounds of Formula I.

The invention provides a compound of Formula I:

##STR00001##

or a pharmaceutically acceptable salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of Formula I, processes for preparing compounds of Formula I, therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS symptoms in a mammal using compounds of Formula I.

The invention provides bifunctional compounds of formula (I) or a pharmaceutically acceptable salt thereof. Formula (I). The compounds cause the degradation of SMARCA2 via the targeted ubiquination of SMARCA2 protein and subsequent proteasomal degradation and are thus useful for the treatment of cancer. The targeting ligand is of formula (TL).

##STR00001##

The present invention relates to a 6-6 bicyclic ring-containing compound derivative and use thereof. The compound according to the present invention acts as a PRMT5 inhibitor, and thus can be effectively used in the prevention or treatment of diseases caused by PRMT5.

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.

A compound of Formula I and formulations including such a compound may be used for the reduction of infestation with ectoparasites, in particular ectoparasites of the insect class, including fleas and mosquitoes, and/or ectoparasites of the arachnid class, including ticks and mites, etc. Methods for controlling ectoparasites and/or formulations including such compounds may include use as a repellent, and/or application to a mammal, e.g., a human, dog, cat, cattle, horse, or sheep, or to an object or a fabric. The form may be a topical formulation, a shampoo composition, a cleansing composition, or a treatment composition, preferably a lotion, cream, ointment, gel, foam, patch, powder, solid, sponge, tape, vapor, paste, tincture, or spray.

A compound of Formula I and formulations including such a compound may be used for the reduction of infestation with ectoparasites, in particular ectoparasites of the insect class, including fleas and mosquitoes, and/or ectoparasites of the arachnid class, including ticks and mites, etc. Methods for controlling ectoparasites and/or formulations including such compounds may include use as a repellent, and/or application to a mammal, e.g., a human, dog, cat, cattle, horse, or sheep, or to an object or a fabric. The form may be a topical formulation, a shampoo composition, a cleansing composition, or a treatment composition, preferably a lotion, cream, ointment, gel, foam, patch, powder, solid, sponge, tape, vapor, paste, tincture, or spray.

The present invention is directed to compounds having the Formulae (Ia), (Ib), (Ic), or (Id); or the Formulae (II), (IIa), (IIb), or (IIc); or the Formulae (III), (IIIa), (IIIb), (IIIc), (IIId), or (IIIe), and pharmaceutically acceptable salts, solvates, clathrates and prodrugs of any Formula thereof, compositions thereof, and methods for the treatment of a condition associated with a dysfunction in proteostasis.