High penetration compositions (HPC) of a parent compound, which are capable of crossing biological barriers with high penetration efficiency. The HPCs are capable of being converted to parent drugs or parent drug-related compounds such as metabolites after crossing one or more biological barriers and thus can render treatments for the conditions that the parent drugs or parent drug-related compounds can. Additionally, the HPCs are capable of reaching areas that their parent drugs or parent drug-related compounds may not be able to access or to render a sufficient concentration at the target areas HPCs of NSAIA, for example, have demonstrated indications such as treating hair loss. A HPC can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

A new set of bench-stable fluoroalkylphosphines that directly convert C—H bonds in pyridine building blocks, drug-like fragments, and pharmaceuticals, into fluoroalkyl derivatives. No pre-installed functional groups or directing motifs are required. The reaction tolerates a variety of sterically and electronically distinct pyridines and is exclusively selective for the 4-position in most cases. The reaction proceeds via initial phosphonium salt formation followed by sp.sup.2-sp.sup.3 phosphorus ligand-coupling, an underdeveloped manifold for C—C bond formation.

A method of administering to a patient in need thereof or contacting with a biological sample, a compound related to Formula I-e ##STR00001##
or pharmaceutically acceptable compositions thereof, is useful to inhibit activity of TLR7/8 or a mutant thereof and/or to treat a TLR7/8-mediated disorder.

A method of administering to a patient in need thereof or contacting with a biological sample, a compound related to Formula I-e ##STR00001##
or pharmaceutically acceptable compositions thereof, is useful to inhibit activity of TLR7/8 or a mutant thereof and/or to treat a TLR7/8-mediated disorder.

The present disclosure relates generally to therapeutic agents that may be useful as inhibitors of Integrated Stress Response (ISR) pathway.

The present disclosure relates generally to therapeutic agents that may be useful as inhibitors of Integrated Stress Response (ISR) pathway.

This method for producing an aromatic astatine compound comprises reacting an aromatic iodonium ylide with astatine to produce an aromatic astatine compound.

The present disclosure provides a compound of Formula (I):

##STR00001##

or a pharmaceutically acceptable salt thereof as described herein. The present disclosure also provides pharmaceutical compositions comprising a compound of Formula (I), processes for preparing compounds of Formula (I), and therapeutic methods for treating inflammatory disease.

Disclosed is a fused ring compound and an application thereof. Disclosed is a fused ring compound represented by formula I, a pharmaceutically acceptable salt, a stereoisomer, a tautomer, an isotope compound, a crystal form, a nitrogen oxide, a solvate, or a solvate of the pharmaceutically acceptable salt thereof. The fused ring compound of the present invention has high P2X4 antagonistic activity, excellent selectivity, low toxicity and excellent metabolic stability.

##STR00001##

Disclosed herein are compounds having a structure of formula (I), compositions and methods useful for the treatment of a disease or infection, such as a viral infection (e.g., Ebola), cancer and obesity: ##STR00001##
wherein A is N or CR.sup.8; Z is ##STR00002## E is selected from optionally substituted alkyl, cycloalkyl, arylalkyl, cycloalkylalkyl, amino, alkoxy, cycloalkyloxy, and cycloalkylamino; R.sup.1 is selected from optionally substituted aryl and heteroaryl, R.sup.2 and R.sup.3 are independently selected from H, deutero, optionally substituted alkyl, haloalkyl, or R.sup.2 and R.sup.3, together with the carbon to which they are bound, combine to form a carbonyl; and R.sup.8 is selected from H, deutero, halo, hydroxyl, cyano, amino, alkyl, alkoxy, carboxy, alkoxycarbonyl, and aminocarbonyl,
provided that E is not ##STR00003##