The present invention relates to Tetracyclic Heterocycle Compounds of Formula ##STR00001##
and pharmaceutically acceptable salts or prodrug thereof, wherein A, X, R.sup.1, R.sup.2, R.sup.3 and Ware as defined herein. The present invention also relates to compositions comprising at least one Tetracyclic Heterocycle Compound, and methods of using the Tetracyclic Heterocycle Compounds for treating or preventing HIV infection in a subject.

Described herein are compounds that are useful in treating a TYK2-mediated disorder. In some embodiments, the TYK2-mediated disorder is an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, or a disorder associated with transplantation.

The present invention provides a compound as represented by formula (1) or a pharmaceutically acceptable salt, a solvate, an active metabolite, a polymorph, an isotope label, an isomer or a prodrug thereof. The present invention also provides a pharmaceutical composition containing the same and the use of the compound and the pharmaceutical composition in preparation of drugs for treating tyrosine kinase-mediated diseases. The compound and the pharmaceutical composition comprising same provided by the present disclosure have significant tyrosine kinase inhibitory activity, can overcome tumor drug resistance, and break through through blood-brain barrier, also have excellent pharmacokinetic properties and excellent oral bioavailability, and can be administered in a small dosage, thereby reducing treatment costs of and possible side effects to a patient. Thus, the application potential is very great.

##STR00001##

The invention relates to modulators of Embryonic Ectoderm Development (EED) and/or Polycomb Repressive Complex 2 (PRC2) useful in the treatment of disorders and diseases associated with EEC and PRC2, being macrocyclic azolopyridine derivatives and compositions thereof of Formula I:

##STR00001##

or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, enantiomer, isomer, or tautomer thereof, wherein X.sub.1, X.sub.2, X.sub.3, A.sub.1, A.sub.2, Y, R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are as described herein.

The invention relates to modulators of Embryonic Ectoderm Development (EED) and/or Polycomb Repressive Complex 2 (PRC2) useful in the treatment of disorders and diseases associated with EEC and PRC2, being macrocyclic azolopyridine derivatives and compositions thereof of Formula I:

##STR00001##

or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, enantiomer, isomer, or tautomer thereof, wherein X.sub.1, X.sub.2, X.sub.3, A.sub.1, A.sub.2, Y, R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are as described herein.

Disclosed is a tricyclic pyrimidinone compound of Formula (I) or a pharmaceutically acceptable salt thereof, which is an entirely new Lp-PLA2 inhibitor useful in treating neurodegeneration-related diseases such as Alzheimer's disease (AD), glaucoma and age-related macular degeneration (AMD), or cardiovascular diseases including atherosclerosis.

Disclosed is a tricyclic pyrimidinone compound of Formula (I) or a pharmaceutically acceptable salt thereof, which is an entirely new Lp-PLA2 inhibitor useful in treating neurodegeneration-related diseases such as Alzheimer's disease (AD), glaucoma and age-related macular degeneration (AMD), or cardiovascular diseases including atherosclerosis.

Disclosed are the macrocyclic compounds having the general Formula (I) and their tautomeric forms, stereoisomers, pharmaceutically acceptable salts, and their combination with suitable medicament, corresponding processes for the synthesis and pharmaceutical compositions and uses of compounds disclosed herein.

##STR00001##

Disclosed are the macrocyclic compounds having the general Formula (I) and their tautomeric forms, stereoisomers, pharmaceutically acceptable salts, and their combination with suitable medicament, corresponding processes for the synthesis and pharmaceutical compositions and uses of compounds disclosed herein.

##STR00001##

Provided herein are small molecule inhibitors of Polycomb Repressive Complex 1 (PRC1) activity, and methods of use thereof for the treatment of disease, including leukemia and other cancers, as well as other diseases dependent on the activity of PRC1.